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Results for “Extracellular Matrix”

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At least 451 records · Page 25Linked to original sources

PubMed1999

Temporal regulation of extracellular matrix components in transition from compensatory hypertrophy to decompensatory heart failure.

OBJECTIVE: Extracellular matrix, particularly type I fibrillar collagen, provides tensile strength that allows cardiac muscle to perform systolic and diastolic functions. Collagen is induced during the transition from compensatory hypertrophy to heart failure. We hypothesized that cardiac stiffness during decompensatory hypertrophy is partly due to a decreased elastin:collagen ratio. MATERIALS AND METHODS: We prepared left ventricular tissue homogenates from spontaneously hypertensive rats (SHR) aged 30-36 weeks, which had compensatory hypertrophy with no heart failure, and from SHR aged 70-92 weeks, which had decompensatory hypertrophy with heart failure. Age- and sex-matched Wistar-Kyoto (WKY) rats were used as normotensive controls. In both SHR groups, increased levels of collagen were detected by immuno-blot analysis using type I collagen antibody. Elastin and collagen were quantitated by measuring desmosine/isodesmosine and hydroxyproline spectrophometrically, respectively. To determine whether the decrease in elastin content was due to increased elastinolytic activity of matrix metalloproteinase-2, we performed gelatin and elastin zymography on left ventricular tissue homogenates from control rats, SHR with compensatory hypertrophy and SHR with heart failure. RESULTS: The elastin:collagen ratio was 0.242 +/- 0.008 in hearts from WKY rats. In SHR without heart failure, the ratio was decreased to 0.073 +/- 0.003 and in decompensatory hypertrophy with heart failure, the ratio decreased to 0.012 +/- 0.005. Matrix metalloproteinase-2 activity was increased significantly in SHR with heart failure compared with controls (P < 0.001). The level of tissue inhibitor of metalloproteinase-4 was increased in compensatory hypertrophy and markedly reduced in heart failure. Decorin was strongly reduced in decompensatory heart failure compared with control hearts. CONCLUSIONS: Since collagen was induced in SHR with heart failure, decorin and elastin were decreased and the ratios of gelatinase A and elastase to tissue inhibitor of metalloproteinase-4 were increased, we conclude that heart failure is associated with adverse extracellular matrix remodeling.

Animals↗

PubMed1993

The extracellular matrix in sarcomatoid carcinomas of the breast.

The distribution of the main extracellular matrix components has been investigated immunohistochemically in four cases of breast sarcomatoid carcinomas. The histogenesis of these tumours is still unclear, but most evidence suggests that the sarcomatous component originates from mesenchymal conversion of carcinomatous cells. We found that carcinomatous portions of the tumours were associated with linear basement membrane-like deposition of laminin, type IV collagen and heparan sulphate proteoglycan that partially circumscribed the epithelial nests. The sarcomatous components produced an extracellular matrix immunoreactive to fibronectin, type I, III and VI collagens and tenascin. However, in two cases, in some sarcomatous areas, focal pericellular staining for antibodies to laminin and type IV collagen was seen. These results indicate that modifications observed in the double tissue component of these tumours involve not only the cell shape and the cytoskeleton, but also the components of the extracellular matrix. The significance of these findings and their relevance in the understanding of the phenotypic pattern changes of these biphasic tumours are discussed.

Aged↗

PubMed1995

Composition of extracellular matrix of type II pulmonary epithelial cells in primary culture.

Type II pulmonary epithelial cells in primary culture synthesize and deposit an extracellular matrix which has reciprocal biological effects on cellular differentiation. The present work establishes conditions for metabolic labeling of matrix constituents and for separation of cells from the associated matrix; it also defines matrix composition, which does not appear to change qualitatively between days 2 and 6 of primary culture. Type II cells synthesize and deposit a spectrum of radiolabeled components on the culture surface. These include fibronectin, laminin, type IV collagen, and plasminogen activator inhibitor-1, along with additional unidentified proteins. Few radiolabeled proteins in medium conditioned by type II cells bind nonspecifically to the culture surface in the absence of cells. Fibroblasts and macrophages, which may contaminate the primary cultures, do not appear to contribute substantially to the type II cell matrix. These results demonstrate that type II cells synthesize and deposit a complex multicomponent extracellular matrix. The work provides a basis for further investigations of bidirectional interactions between type II cells and the extracellular matrix.

Animals↗

PubMedDate not supplied

Immunohistochemical expression of extracellular matrix proteins and adhesion molecules in pancreatic carcinoma.

BACKGROUND/AIMS: Carcinoma invasion and metastasis in general involve multiple steps including dynamic changes in the composition and structure of extracellular matrix proteins and cell surface receptors. In the present study, the usually highly invasive carcinoma of the pancreas was investigated regarding the expression of various extracellular matrix proteins and their corresponding integrin receptors, as well as E-cadherin. METHODOLOGY: Phenotypic expression of various markers was investigated immunohistochemically in frozen sections of 16 pancreatic carcinomas and normal pancreatic tissue. RESULTS: An irregular and discontinuous deposition of type IV collagen and laminin in the basement membrane was found in cancer tissue and a pronounced desmoplastic reaction with deposition of type I, type III, and type IV collagen in the tumor stroma. In contrast, the noninvolved pancreas showed an intact basement membrane and a sparse stroma. The collagen type IV and laminin receptors alpha 2, alpha 3, and beta 1 integrin subunits were expressed on pancreatic cancer cells but not the alpha 6 integrin subunit normally present on epithelial cells, suggesting anchorage independence of the carcinoma cells. An increased capacity for cancer cell motility was suggested by the abundant expression of the "antiadhesive" extracellular matrix proteins, tenascin and vitronectin close to the cancer cells, and the expression of cell surface receptors such as alpha v (vitronectin-binding). Expression of the alpha 4 integrin subunit was also increased on cancer cells. CONCLUSIONS: The distribution of extracellular matrix proteins and the cell surface immune phenotype differed in pancreatic carcinoma as compared to normal pancreatic tissue. The present findings substantiate the notion that disseminated growth of highly malignant carcinomas of the pancreas reflects an invasive interaction of the tumor cells with extracellular matrix proteins of a well-established stroma. Similar findings were observed regardless of tumor histology and patient survival time.

Adenocarcinoma↗

PubMed1993

Assessment of the fibrogenetic activity in chronic pancreatitis. The role of circulating levels of extracellular matrix components.

Determination of circulating levels of extracellular matrix components has been proposed as a reliable method to assess the activity of fibrogenetic processes. Therefore, we aimed to analyze circulating levels of laminin, fibronectin, and procollagen III peptide (PIIIP) in patients with chronic pancreatitis (CP) and to correlate them with the morphological and functional stage, and duration of the disease. Thirty patients with CP and 18 healthy controls were studied. Serum PIIIP concentrations (RIA), but not fibronectin (RID) and laminin (RIA), were abnormally high in 8 patients with CP. No correlation was found between circulating levels of extracellular matrix components and both functional and morphological stage and duration of CP. Nevertheless, patients with elevated serum PIIIP levels tend to have a more advanced CP (morphological and functional changes) than those with normal levels after a similar duration of the disease. We hypothesize that whereas functional and morphological findings reflect the cumulative effect of chronic inflammation on the pancreas, serum PIIIP concentrations would reflect the activity of the fibrogenetic process within the gland at the time of sampling. The results shown in the present study may be considered a starting point for longitudinal studies that examine the relationship between serum PIIIP or other markers for fibrogenetic activity and evolution of CP.

Adult↗

PubMed2002

The class A scavenger receptor binds to proteoglycans and mediates adhesion of macrophages to the extracellular matrix.

The class A scavenger receptor (SR-A) binds modified lipoproteins and has been implicated in cholesterol ester deposition in macrophages. The SR-A also contributes to cellular adhesion. Using SR-A(+/+) and SR-A(-)/- murine macrophages, we found SR-A expression important for both divalent cation-dependent and -independent adhesion of macrophages to the human smooth muscle cell extracellular matrix. The SR-A mediated 65 and 85% of macrophage adhesion to the extracellular matrix in the presence and absence of serum, respectively. When EDTA was added to chelate divalent cations, the SR-A mediated 90 and 95% of the macrophage adhesion without and with serum, respectively. SR-A-mediated adhesion to the extracellular matrix was prevented by fucoidin, an SR-A antagonist. Biglycan and decorin, proteoglycans of the extracellular matrix, were identified as SR-A ligands. Compared with control cells, Chinese hamster ovary cells expressing the SR-A showed 5- and 6-fold greater cell association (binding and internalization) of (125)I-decorin and -biglycan, respectively. In competition studies, unlabeled proteoglycan or fucoidin competed for binding of (125)I-labeled decorin and -biglycan, and biglycan and decorin competed for the SR-A-mediated cell association and degradation of (125)I-labeled acetylated LDL, a well characterized ligand for the SR-A. These results suggest that the SR-A could contribute to the adhesion of macrophages to the extracellular matrix of atherosclerotic plaques.

Animals↗

PubMed1996

Cardiogel: a biosynthetic extracellular matrix for cardiomyocyte culture.

Tissue-cultured neonatal cardiomyocytes can be successfully maintained in culture on a variety of extracellular matrix components such as laminin, fibronectin, and interstitial collagens (Types I and III). In vivo, however, cardiomyocytes (as well as many other cells) exist in a highly complex extracellular matrix environment composed of, in addition to the above three components, other proteins, proteoglycans, and growth factors. We have developed a procedure for culturing cardiomyocytes on a naturally occurring complete extracellular matrix, Cardiogel. This substrate, synthesized by cardiac fibroblasts, contains laminin, fibronectin. Types I and III collagen, and proteoglycans. When compared to cardiomyocytes grown on laminin alone or fibronectin alone, Candiogel-supported cardiomyocytes adhere more rapidly after plating, exhibit spontaneous contractility earlier, undergo cytoskeletal and myofibrillar differentiation earlier, and grow larger than their counterparts. We suggest that their superior growth characteristics reflect the synergistic effect of numerous extracellular matrix components signals in Cardiogel transduced by the cardiomyocyte cytoskeletal elements.

Animals↗

PubMed2000

Carboxypeptidase Z is present in the regulated secretory pathway and extracellular matrix in cultured cells and in human tissues.

Carboxypeptidase Z (CPZ) is a newly reported member of the metallocarboxypeptidase gene family, but unlike other members of this family, CPZ contains an N-terminal domain that has amino acid sequence similarity to Wnt-binding proteins. In order to gain insights as to the potential function of CPZ, the intracellular localization of this protein was determined in cell culture and in human tissues. When expressed in the AtT-20 mouse pituitary cell line, CPZ protein is routed to the regulated secretory pathway and secreted upon stimulation. A fraction of the secreted CPZ remains associated with the extracellular matrix. Endogenous CPZ in the PC12 rat pheochromocytoma cell line is also associated with the extracellular matrix. In human placenta, CPZ is present within invasive trophoblasts and in the surrounding extracellular space, indicating an association with extracellular matrix. CPZ is also present in amnion cells, but is not readily apparent in the extracellular matrix of this cell type. A human adenocarcinoma of the colon shows expression of CPZ in the extracellular matrix adjacent to malignant cells. Taken together, CPZ appears to be a component of the extracellular matrix in some cell types, where it may function in the binding of Wnt.

Animals↗

PubMed1998

Expression of plasminogen activator pla of Yersinia pestis enhances bacterial attachment to the mammalian extracellular matrix.

The effect of the plasminogen activator Pla of Yersinia pestis on the adhesiveness of bacteria to the mammalian extracellular matrix was determined. Y. pestis KIM D27 harbors the 9.5-kb plasmid pPCP1, encoding Pla and pesticin; the strain efficiently adhered to the reconstituted basement membrane preparation Matrigel, to the extracellular matrix prepared from human lung NCI-H292 epithelial cells, as well as to immobilized laminin. The isogenic strain Y. pestis KIM D34 lacking pPCP1 exhibited lower adhesiveness to both matrix preparations and to laminin. Both strains showed weak adherence to type I, IV, and V collagens as well as to human plasma and cellular fibronectin. The Pla-expressing recombinant Escherichia coli LE392(pC4006) exhibited specific adhesiveness to both extracellular matrix preparations as well as to laminin. The Pla-expressing strains showed a low-affinity adherence to another basement membrane component, heparan sulfate proteoglycan, but not to chondroitin sulfate proteoglycan. The degradation of radiolabeled laminin, heparan sulfate proteoglycan, or human lung extracellular matrix by the Pla-expressing recombinant E. coli required the presence of plasminogen, and degradation was inhibited by the plasmin inhibitors aprotinin and alpha2-antiplasmin. Our results indicate a function of Pla in enhancing bacterial adhesion to extracellular matrices. Y. pestis also exhibits a low level of Pla-independent adhesiveness to extracellular matrices.

Bacterial Adhesion↗

PubMed1996

Expression and function of receptors for extracellular matrix proteins in human ductal adenocarcinomas of the pancreas.

Extracellular matrix proteins (ECM) may influence cellular differentiation via their receptors, the integrins. We recently presented evidence that ductal adenocarcinomas of the pancreas are able to produce ECM in vitro and in vivo (Br J Cancer 1994;49:144-51). This study examines whether pancreatic carcinoma cells are able to interact with ECM by expressing functionally active integrins. In eight human pancreatic tumor cell lines (AsPC-1, BxPC-3, CAPAN-1 and -2, PANC, PaTu-2, -3, and -44) and six xenografted tumors RNA and protein expression of integrin subunits alpha 5 (fibronectin receptor), alpha 6 (laminin receptor), and alpha V (vitronectin receptor) was investigated. In addition, alpha 1-alpha 6 and alpha V as well as beta 1-beta 4 were studied by fluorescence-activated cell sorter analysis. Integrin function was tested by attachment assays. alpha 2, alpha 3, alpha 5, alpha 6, and alpha V as well as beta 1, beta 3, and beta 4 were expressed, at both the RNA and the protein level, by all pancreatic tumors in vitro and in vivo. The tumor cell lines showed dose dependent adhesion to collagen, fibronectin, and laminin. Integrin expression could be modulated in part by serum depletion. None of the tumors showed alpha 1, alpha 4, and beta 2. Tumor cell differentiation or production of ECM was not correlated with integrin expression. Pancreatic ductal adenocarcinomas express a certain pattern of functionally active integrins that enable interaction with most matrix proteins, e.g., collagen, fibronectin, and laminin. Pancreatic adenocarcinomas possess both the ligands and the receptors of the extracellular matrix network. We speculate that through both classes of molecules, the tumor cells may bind to fibroblasts and probably stimulate their growth. However, it remains unclear whether and how integrin-ECM interaction exerts an influence on tumor cell differentiation.

Animals↗

PubMed1994

The extracellular matrix in hepatocellular carcinoma shows different localization patterns depending on the differentiation and the histological pattern of tumors: immunohistochemical analysis.

This study investigated cells producing type I, III, and IV collagens, laminin, and fibronectin, the major components of the extracellular matrix, and compared their localization patterns in relation to the grade of tumor differentiation and the histological pattern of hepatocellular carcinoma. Type I, III, and IV collagens, laminin, and fibronectin were produced by tumor, endothelial, and Ito cells. Regarding their localization pattern in relation to the histological pattern of tumors, although the extracellular matrix was present in the subendothelial spaces of sinusoids in every histological pattern, the localization of these components in the intercellular spaces of tumor cells was most marked in hepatocellular carcinoma with a compact pattern. These results suggest that the extracellular matrix produced by tumor, endothelial, and Ito cells is deposited in appropriate positions in hepatocellular carcinoma to sustain the tissue structure showing different histological patterns. In relation to the grade of tumor differentiation, in most cases, Type I, III, and IV collagens and fibronectin were present in the subendothelial spaces of sinusoids and the intercellular spaces of some tumor cells, while little laminin was observed in well-differentiated small hepatocellular carcinoma (less than 10 mm diameter). In undifferentiated hepatocellular carcinoma, little extracellular matrix was observed, except around vessels. These results suggest that sinusoidal capillarization may not yet have occurred in the early stage of hepatocarcinogenesis, although it develops as the tumors increase in size and the tumor cells dedifferentiate. In undifferentiated hepatocellular carcinoma, tumor cells are too atypical to produce each extracellular matrix component.

Adult↗

PubMed1994

Tenascin is synthesized and secreted by rat mesangial cells in culture and is present in extracellular matrix in human glomerular diseases.

Tenascin (TN) is a large oligomeric protein recently described as a component of the extracellular matrix. The distribution of TN in adult kidney tissue has not been adequately evaluated, but preliminary data have suggested that TN is variably seen in rare mesangial areas and in stroma surrounding some tubules. The enlargement of the mesangial matrix (mesangial sclerosis) is a common feature of many renal diseases and is thought to be partially related to oversynthesis of the normal components of the mesangial matrix (collagen type IV, laminin, fibronectin, and heparan sulfate proteoglycans) by mesangial cells. However, the possibility that mesangial cells are also the source of other extracellular matrix proteins that participate in the process of mesangial sclerosis has not been explored. In this study, the synthesis of TN by cultured rat mesangial cells was documented by the following observations: (1) Northern hybridization of total RNA extracted from mesangial cells showed two distinct species of TN mRNA; (2) immunoblotting of the protein extracted from the conditioned medium demonstrated four TN protein bands; (3) immunoblotting of the protein extracted from the mesangial cell lysate demonstrated at least four TN protein bands; and (4) immunohistochemical techniques identified TN within the cytoplasm of mesangial cells and in the surrounding extracellular matrix.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1998

Binding of insulin-like growth factor (IGF)-binding protein-5 to smooth-muscle cell extracellular matrix is a major determinant of the cellular response to IGF-I.

Insulin-like growth factor-binding protein-5 (IGFBP-5) has been shown to bind to fibroblast extracellular matrix (ECM). Extracellular matrix binding of IGFBP-5 leads to a decrease in its affinity for insulin-like growth factor-I (IGF-I), which allows IGF-I to better equilibrate with IGF receptors. When the amount of IGFBP-5 that is bound to ECM is increased by exogenous addition, IGF-I's effect on fibroblast growth is enhanced. In this study we identified the specific basic residues in IGFBP-5 that mediate its binding to porcine smooth-muscle cell (pSMC) ECM. An IGFBP-5 mutant containing alterations of basic residues at positions 211, 214, 217, and 218 had the greatest reduction in ECM binding, although three other mutants, R214A, R207A/K211N, and K202A/R206N/R207A, also had major decreases. In contrast, three other mutants, R201A/K202N/R206N/R208A, and K217N/R218A and K211N, had only minimal reductions in ECM binding. This suggested that residues R207 and R214 were the most important for binding, whereas alterations in K211 and R218, which align near them, had minimal effects. To determine the effect of a reduction in ECM binding on the cellular replication response to IGF-I, pSMCs were transfected with the mutant cDNAs that encoded the forms of IGFBPs with the greatest changes in ECM binding. The ECM content of IGFBP-5 from cultures expressing the K211N, R214A, R217A/R218A, and K202A/R206N/R207A mutants was reduced by 79.6 and 71.7%, respectively, compared with cells expressing the wild-type protein. In contrast, abundance of the R201A/K202N/R206N/R208A mutant was reduced by only 14%. Cells expressing the two mutants with reduced ECM binding had decreased DNA synthesis responses to IGF-I, but the cells expressing the R201A/K202N/R206N/R208A mutant responded well to IGF-I. The findings suggest that specific basic amino acids at positions 207 and 214 mediate the binding of IGFBP-5 to pSMC/ECM. Smooth-muscle cells that constitutively express the mutants that bind weakly to ECM are less responsive to IGF-I, suggesting that ECM binding of IGFBP-5 is an important variable that determines cellular responsiveness.

Animals↗

PubMed1992

Immunohistochemical study of extracellular matrix in acute galactosamine hepatitis in rats.

A single injection of D-galactosamine hydrochloride induces acute self-limiting liver disease in rats that morphologically resembles drug-induced hepatitis in human beings. In this immunohistochemical study we examined the localization and expression of the hepatic extracellular matrix components fibronectin, laminin, collagen type I, collagen type III and collagen type IV and of the cell surface receptors (integrins) for fibronectin and laminin. Sections of liver tissue obtained at intervals of 6, 12, 18, 24, 30, 36, 48 and 72 hr and 7 and 21 days after galactosamine administration were immunostained with a panel of polyclonal monospecific antibodies and studied independently by two of us. Fibronectin was the first extracellular matrix component found to be increased, 12 hr after galactosamine injection, followed by collagen type III, and, in a later phase, collagen type IV, type I and laminin. Increased deposition of extracellular matrix was found in areas with liver cell necrosis and along sinusoids. Extracellular matrix immunoreactivity reached a maximum at 36 to 48 hr and decreased thereafter to preinjury levels 3 wk after galactosamine. Immunostaining for the fibronectin and laminin receptors revealed tissue localization identical to that of their ligands. However, the intensity of staining was opposite of that for the extracellular matrix, with a decrease of immunoreactivity after 24 to 48 hr. The observed sequence of changes in hepatic extracellular matrix proteins after galactosamine injection resembles the repair reaction in other tissues and may reflect the particular function that each carries out during the process of liver healing after toxic injury.

Acute Disease↗

PubMed1988

Three-dimensional organization of the extracellular matrix secreted by cultured rat smooth muscle cells.

Specific interactions between cells and the extracellular matrix (ECM) in which they are embedded play a vital role in tissue organization. In recent years, many of the individual components of the extracellular matrix have been isolated and their molecular structures elucidated, but the detailed topography of most extracellular matrices, as they are deposited by cells, is still largely unknown. In this study, the insoluble extracellular matrix produced by cultured rat vascular smooth muscle cells has been characterized morphologically using high-resolution electron microscopy of rotary platinum replicas. These cells grew as flat sheets in culture, secreting their matrix laterally and basally. The matrix was composed of a cross-linked fibrillar meshwork. Some fine fibers (10 to 15 nm in diameter) were naked, but most of the filamentous mesh was covered with coarse granular material. Limited digestion with trypsin or pancreatic elastase removed most of this coating, indicating that the granules were glycoproteins and proteoglycans. Another subset of matrix fibrils (20 to 40 nm in diameter) was identified as type I collagen by direct comparison with purified bovine skin collagen. In addition to exposing the underlying filamentous substructure of the matrix, protease treatment also revealed large, straight fiber bundles and globules of amorphous material suspended in the filamentous web. This novel view of a complex matrix promises to provide spatial information that will be useful in future studies of cell interactions with the ECM.

Ammonium Hydroxide↗

PubMed2001

Altered expression of extracellular matrix and proteinases in Noble rat prostate gland after long-term treatment with sex steroids.

BACKGROUND: Interactions between the epithelial cells and stromal tissues, which include the epithelial basement membrane, extracellular matrix, inducible factors, and various cell types, are believed to play a significant role in prostate gland carcinogenesis. Remodeling of extracellular matrix and degradation of basement membrane are the prerequisites for tumor cell invasion, and these changes are correlated with the expression of various proteinases. METHODS: The present study examined the alterations of epithelial basement membrane, extracellular matrix, and proteinase activities in the Noble rat prostate gland after long-term treatments with androgen and estrogen (T+DES or T+E(2) for 4-12 months) by histochemistry, immunohistochemistry, electron microscopy, and gelatin-gel zymography. RESULTS: After hormonal treatments, defects of epithelial basement membranes, such as focal disruption, diffuse staining and multilayering, were observed by histochemistry and immunohistochemistry in the dysplastic and neoplastic lesions induced in the lateral (LP) and ventral prostates (VP) but not in dorsal prostate (DP). An increase in the amount of extracellular matrix components, including hyaluronan (HA), chondroitin sulfate proteoglycan (CSPG) and tenascin, in the stroma of hormone-treated LP and VP was revealed by histochemistry and immunohistochemistry. Positive immunolabeling of matrix metalloproteinases 2 (MMP-2) and 9 (MMP-9) was detected in the fibromuscular layer surrounding the adenoma and adenocarcinoma induced in LP and VP after treatments with steroids for over 9-12 months. Zymography also detected an increase in activities of proteinases of apparent MW 120, 90, 86 and 68 kDa in the hormone-treated LP and VP, and these proteinases were characterized as metalloproteinases. In addition, two serine proteinases of MW 100 and 30 kDa were identified as being overexpressed in the hormone-treated LP and VP. Compared to LP and VP, there was no significant change in the proteinase activities in the hormone-treated DP. CONCLUSIONS: The present study demonstrated that the epithelial basement membrane and stromal extracellular matrix were altered in dysplastic and neoplastic Noble rat prostates. Since HA and CSPG (or their complexes) are highly anionic molecules, their increased accumulation in the altered prostatic stroma would tend to hydrate this tissue. This would create an environment more favorable for tumor growth and invasion. These morphological changes were also correlated with the concurrent increase in gelatinolytic proteinase activities induced in these prostates. The results suggest that the remodeling of the stromal tissue might play a role in the early stage of prostate carcinogenesis as shown in the Noble rat model.

Adenocarcinoma↗

PubMed1990

Expression and structure of human SPARC transcripts: SPARC mRNA is expressed by human cells involved in extracellular matrix production and some of these cells show an unusual expression pattern.

A mouse SPARC cDNA clone was used to elucidate the expression of SPARC mRNA in normal diploid human cells as well as in tumor cells. Among 40 cell lines examined, 19 showed expression. The mRNA transcribed by the majority of the expressors are 2.1 kb with a trace amount of 3 kb. However, three cell types, undifferentiated basal keratinocytes, their differentiated derivatives, and breast adenocarcinoma cells, showed an expression pattern distinct from the typical one, having abundant 3-kb mRNA but no detectable 2.1-kb mRNA. The mRNA was translated and the product secreted. This expression pattern was not observed before in human cells and was not found in tumor cells of keratinocytes, squamous carcinoma cells, or many other adenocarcinoma cells. We showed by Northern hybridization that the SPARC-expressing melanocytic melanoma cell lines produced laminin, a component of extracellular matrix. Other cell types expressing the SPARC mRNA were also reported to synthesize extracellular matrix components. Thus, our results indicate an association between SPARC gene expression and production of extracellular matrix. However, the opposite is not true since non-SPARC-producers may or may not produce extracellular matrix. For example, A431 cell line, which does not express SPARC mRNA, is known to produce extracellular matrix components while the normal diploid melanocytes and undifferentiated embryonal carcinoma cells, which do not express SPARC mRNA, do not produce extracellular matrix component.

Adenocarcinoma↗

PubMed1991

Extracellular matrix molecules in development and regeneration of the leech CNS.

As neurons grow to their targets their processes elongate, branch and form specialized endings into which are inserted appropriate ion channels. Our aim has been to analyse the role of the extracellular matrix molecules laminin and tenascin in inducing growth and in determining the form and physiological properties of growing neurites. A preparation in which development and regeneration can be followed at the cellular and molecular level in the animal and in tissue culture is the central nervous system (CNS) of the leech. In leech extracellular matrix (ECM) both laminin and tenascin are present; the molecules are structurally similar but not identical to their vertebrate counterparts. Tenascin extracted from leech ECM shows a typical hexabrachial structure whereas laminin shows a typical cruciform structure in rotary shadowed preparations. Leech laminin purified by means of a monoclonal antibody is a molecule of about 1000 kDa, with a polypeptide composition of 340, 200, 180 and 160 kDa. Substrates that contain tenascin or laminin produce rapid and reliable outgrowth of neurites by identified cells. A remarkable finding is that the outgrowth pattern produced by an individual neuron depends in part on its identity, in part on the substrate upon which it is placed. For example, a Retzius cell grows in a quite different configuration and far more rapidly on laminin substrate than does another type of neuron containing the same transmitter (serotonin); and the pattern of outgrowth of the Retzius cell is different on laminin and on the plant lectin Con A (concanavalin A). Thus Con A induces the growth of processes that are shorter, thicker, more curved and contain fewer calcium channels than those grown on laminin. To determine whether laminin can also influence neurite outgrowth in the animal, immunocytological techniques have been used to follow its distribution in the extracellular matrix of normal, developing and regenerating leech CNS. In adult leeches neuronal processes in the CNS are not in contact with laminin which is confined to the surrounding extracellular matrix. In embryos however, laminin staining appears between ganglionic primordia along the pathways that neurons will follow. Similarly, after injury to the adult CNS, laminin accumulates at the very sites at which sprouting and regeneration begin. How the laminin becomes redistributed to appear in the region of injury has not yet been established. Together these findings suggest a key role for laminin and for other extracellular matrix molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗