Biomedical subjects

H Autio-Harmainen

Publications and source records attributed to H Autio-Harmainen.

At least 37 records · Page 2Linked to original sources

PubMed1996

Expression of the tissue metalloproteinase inhibitors TIMP-1 and TIMP-2 in malignant fibrous histiocytomas and dermatofibromas as studied by in situ hybridization and immunohistochemistry.

The expression of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) was studied in eight malignant fibrous histiocytomas (MFH) and in eight dermatofibromas (DF) using in situ hybridization methods (ISH). Immunohistochemical stainings were also performed using corresponding antibodies to TIMP-1 and TIMP-2. In ISH the neoplastic cells of MFHs showed a high level of expression for both TIMP-1 and TIMP-2 mRNAs. The cells usually expressed similarly both TIMPs, except for osteoclast-like giant cells, which showed a distinct signal for TIMP-2 but not for TIMP-1. A distinctly lower level of both TIMP-1 and TIMP-2 mRNAs was seen in DFs. Immunohistochemical stainings were concordant with the results obtained by ISH. The findings suggest that the behavior of MFHs and DFs is not directly or solely dependent on the quantity of type IV collagenase inhibitors. The increased TIMP synthesis in MFHs might represent a chaotic response of malignant cells to increased matrix degradation. Alternatively, it may reflect a deranged communication between type IV collagenases and TIMPs in malignant tissues.

Adult↗

PubMed1996

Intraductal papilloma as a cause of a parotid duct cyst. A case report.

A case is presented of a rare intraductal papilloma being found simultaneously with a parotid duct cyst, which is a relatively common parotid disorder. The papilloma most probably played a significant role in the obstruction of the duct and thus caused the ductal cyst. Intraductal papillomas have been mostly described in minor salivary glands, but are rare in the parotid gland.

Cysts↗

PubMed1996

mRNA expressions of TIMP-1, -2, and -3 and 92-KD type IV collagenase in early human placenta and decidual membrane as studied by in situ hybridization.

Cytotrophoblasts of early placenta invade the decidual membrane, gestational endometrium, and spiral arteries during early pregnancy. Unlike tumor invasion, this physiological invasion is well controlled, although its molecular mechanisms are largely unknown. We have previously shown that cytotrophoblasts synthesize significant mRNAs for 72-KD Type IV collagenase, laminin, and Type IV collagen, proteins implicated in extracellular matrix turnover and migration. In this study we used in situ hybridization and immunohistochemistry to investigate the mRNA expression pattern of 92-KD Type IV collagenase and the matix metalloproteinase inhibitors TIMP-1, TIMP-2, and TIMP-3 in early human placenta and decidual membrane. mRNAs for 92-KD Type IV collagenase, TIMP-1, TIMP-2, and TIMP-3 were found in the cells of cytotrophoblastic columns, the endothelial and fibroblastic stromal cells of villi, and the large decidualized cells of decidual membrane. TIMP-1 expression was notably accentuated in the fibroblasts of fibrotic villi. In the decidual membrane, the signals for 92-KD Type IV collagenase and TIMP-1 mRNA were particularly strong around the glandular structures. The trophoblastic epithelium of villi and the epithelial cells of decidual glands showed a signal for 92-KD Type IV collagenase and TIMP-2, but not for TIMP-1 or TIMP-3. The coincidental expression of the proteolytic 92-KD Type IV collagenase and inhibitors TIMP-1, TIMP-2, and TIMP-3 generally in the same cells suggests that the activity of 92-KD Type IV collagenase, which is regulated by TIMPs, plays an important role in placental tissue organization and in the invasion of trophoblastic cells into the uterine wall.

Collagenases↗

PubMed1995

Immuno-electron-microscopic localization of types III pN-collagen and IV collagen, laminin and tenascin in developing and adult human spleen.

The distribution of the extracellular matrix proteins types III pN-collagen and IV collagen, laminin and tenascin was investigated in fetal, infant, and adult human spleens by using immuno-electron microscopy. The presence of type III pN-collagen was assessed by using an antibody against the aminoterminal propeptide of type III procollagen. All the proteins other than type III pN-collagen were found in reticular fibers throughout development. In the white pulp of the fetus aged 16 gestational weeks, only an occasional type III pN-collagen-containing fibril was present, although type III pN-collagen was abundant in the reticular fibers of the red pulp. Conversely, in adults, most of the reticular fibers of the white pulp, but not of the red pulp, were immunoreactive for type III pN-collagen. Ring fibers, the basement membranes of venous sinuses, were well developed in both infant and adult spleens. The first signs of their formation could be seen as a discontinuous basement membrane, which was immunoreactive for type IV collagen, laminin, and tenascin in the fetus aged 20 gestational weeks. Intracytoplasmic immunoreactivity for all the proteins studied was visible in the mesenchymal cells of the fetus aged 16 gestational weeks and in the reticular cells of the older fetuses, which also showed labeling for type IV collagen and laminin in the endothelial cells. The results suggest that proteins of the extracellular matrix are produced by these stationary cells.

Adult↗

PubMed1995

Increased collagen synthesis in psoriasis in vivo.

Psoriasis is an inflammatory skin disease of unknown a etiology which also involves changes in dermal elements. Previous in vitro studies have shown an increased collagen synthesis rate in cultured fibroblasts. In this study collagen synthesis was studied in vivo in the uninvolved skin of psoriatic patients using a newly developed method in which collagen propeptides were measured in suction blister fluid. Both type I and type III collagen synthesis rates, as measured in terms of the carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP), were increased about two-fold in uninvolved psoriatic skin as compared with controls, the mean level of PICP being 870 and 457 micrograms, respectively (P < 0.001), and of PIIINP being 294 and 124 micrograms, respectively (P < 0.01). The increased collagen synthesis rate was also confirmed by in situ hybridization using specific probes. Collagen mRNAs were found to be particularly abundant in psoriatic patients, who also demonstrated a high collagen synthesis rate when assayed by measuring collagen propeptides. The increased rate of collagen synthesis in the uninvolved psoriatic skin seemed not to be related to the severity of the disease or to various treatments such as UVB, PUVA, retinoids or cytostatic drugs, but seemed more likely to be due to the psoriasis itself. Interestingly, skin thickness was not increased in the patients with psoriasis, even though collagen synthesis was markedly elevated, perhaps suggesting that in psoriasis the turnover rate of collagen is enhanced.

Adult↗

PubMed1995

Distribution of type XV collagen transcripts in human tissue and their production by muscle cells and fibroblasts.

Type XV collagen is a recently identified member of the diverse family of collagens, its structure being characterized by extensive interruptions in the collagenous sequences. A combination of Northern blot hybridization of fetal and adult human tissues and in situ hybridization analyses of a fetus with Down's syndrome, several placentas, and adult skin were used to localize expression of its mRNAs. Northern blot analysis revealed marked expression in heart, skeletal muscle, and placenta tissues and moderate levels in the kidney and pancreas. Clear in situ hybridization signals were detected in fibroblasts and endothelial cells in all tissues studied. Examination of fetal heart, skeletal muscle, and smooth muscle tissues showed that the high type XV collagen mRNA level in the muscle RNA was localized not only to fibroblasts residing in the endomysium but also to myoblasts. Interestingly, type XV collagen mRNAs were also synthesized by certain epithelial cells in kidney, lung, pancreas, and placenta. It was the morphologically immature glomeruli in the kidney and the lower parts of the nephron, especially the collecting ducts, that contained these mRNAs but not the mature glomeruli or proximal tubules, suggesting differences in expression during development. These findings indicate a wide distribution of type XV collagen transcripts, the main producers being mesenchymally derived cells, particularly muscle cells and fibroblasts.

Adult↗

PubMed1994

72 KD and 92 KD type IV collagenase, type IV collagen, and laminin mRNAs in breast cancer: a study by in situ hybridization.

It is widely accepted that basement membrane (BM) components are synthesized by epithelial cells and that production of BM-degrading proteases by cancer cells is necessary for invasive growth. In this study we used nucleic acid in situ hybridization (ISH) to investigate the presence of mRNAs for 72 KD and 92 KD Type IV collagenase, alpha 1 (IV) chain of Type IV collagen, and laminin B1 chain in 20 breast carcinomas of various histological types. The mRNA signals for 72 KD Type IV collagenase, Type IV collagen, and laminin were much more abundant in stromal fibroblasts and endothelial cells than in carcinoma cells. The signal for 92 KD Type IV collagenase mRNA was strong in carcinoma cells and considerably weaker in stromal fibroblasts and endothelial cells. Labeling for 72 KD and 92 KD Type IV collagenase mRNA was also found in benign fibroadenomas and for 92 KD Type IV collagenase in non-neoplastic ducts and acini. The results indicate that stromal cells have a more important role in the synthesis and degradation of BMs in breast carcinomas than previously thought and that production of these enzymes is not restricted to malignancy.

Adult↗

PubMed1994

Rat 17 beta-hydroxysteroid dehydrogenase type 1: primary structure and regulation of enzyme expression in rat ovary by diethylstilbestrol and gonadotropins in vivo.

17 beta-Hydroxysteroid dehydrogenase (17HSD) catalyzes the reversible conversion of estrone into estradiol. The complementary DNA (cDNA) coding for rat 17HSD type 1 was cloned from a commercial rat ovarian cDNA library, using human 17HSD type 1 cDNA as a probe. The nucleotide sequence extends for 1160 basepairs (bp), including 1035 bp of open reading frame, a stop codon, and 125 bp of 3'-untranslated sequence. The cDNA encodes a protein of 344 amino acids, with a calculated molecular mass of 36,967 daltons. The overall amino acid identity and similarity between rat and human 17HSD type 1 enzymes are 68% and 80%, respectively. Immunohistochemistry and in situ and Northern hybridizations were used to study regulation of the enzyme in rat ovary in vivo. Enzyme expression was detected in granulosa cells only, whereas no expression was observed in stromal or thecal cells. The enzyme was almost undetectable in ovaries from immature hypophysectomized rats. After 2-day treatment with recombinant FSH (recFSH), an induction of 17HSD type 1 expression was observed in granulosa cells of growing antral follicles. During 5 days of diethylstilbestrol (DES) treatment, a time-dependent increase in developing follicles was observed, showing strong expression of 17HSD type 1 in granulosa cells. Treatment with recFSH for 2 days in DES-primed animals resulted in down-regulation of ovarian enzyme expression. This reduction of enzyme expression was associated with luteinization of the follicles. hCG treatment of recFSH- or DES- plus recFSH-primed animals further induced luteinization, resulting in strong down-regulation of 17HSD type 1 expression. The enzyme was not detected in corpora lutea. The data show that 17HSD type 1 expression in rat ovary is regulated by gonadotropins and estrogens. The results suggest that expression of 17HSD type 1 and that of cytochrome P450 aromatase are regulated by distinct mechanisms, and 17HSD type 1 may be down-regulated earlier than P450 aromatase during luteinization, limiting estradiol biosynthesis in luteinizing granulosa cells in rat ovary.

17-Hydroxysteroid Dehydrogenases↗

PubMed1994

UV irradiation induces the expression of gelatinases in human skin in vivo.

UV irradiation results in marked changes in skin connective tissue, such as degeneration of collagen, and abnormal elastosis. The mechanism of connective tissue damage by UV has not been clarified in detail. In the present study the mechanism of actinic damage was studied by assaying gelatinases, 72-kDa (MMP-2) and 92-kDa (MMP-9), from suction blister fluids induced on patients who had received either UVB or PUVA treatments. The results indicate that both UVB and PUVA increase the levels of gelatinases in human skin. By in situ hybridization, it was also possible to show that UV irradiation induced increased levels of gelatinase mRNAs in fibroblasts. Furthermore, in samples from severe actinic damage, gelatinase mRNAs were abundantly present, suggesting that gelatinases may contribute to photodamage.

Adult↗

PubMed1994

Expression of matrix metalloproteinase-2 and -9 during early human wound healing.

BACKGROUND: During wound healing, keratinocytes detach from the basement membrane and migrate to cover the exposed connective tissue. Subsequently, the wound clot is degraded gradually and replaced by the epithelial cells and the granulation tissue. Both of these processes are likely to be affected by matrix-modifying enzymes. Type IV collagenases are members of the matrix metalloproteinase family (MMP), which are known to degrade several matrix components. The aim of this study was to investigate the expression of MMP-2 and MMP-9 (72-kd and 92-kd type IV collagenases, respectively) during early human wound healing. EXPERIMENTAL DESIGN: Experimental wounds were created in human oral mucosa and biopsies were taken 1, 3, and 7 days after wounding. In situ hybridization on paraffin sections was used for the detection of messenger RNAs coding for MMP-2 and MMP-9, and the secretion of MMPs into the oral cavity after wounding was followed by zymography. Regulation of MMP-2 and MMP-9 expression by cytokines was studied using cultured mucosal keratinocytes, gingival fibroblasts, and wound granulation tissue fibroblasts. RESULTS: By in situ hybridization, the expression of MMP-2 was localized in the connective tissue fibroblasts and endothelial cells during all phases of wound healing. Mucosal epithelium was practically negative for MMP-2 expression. MMP-9 messenger RNA was found in mucosal epithelium on days 1, 3, and 7. A strong signal was localized in basal and suprabasal cell layers in the nonwounded area, while only the basal cell layer was MMP-9 positive in the migrating epithelial sheet. Seven days after wounding, granulation tissue exhibited an unusually strong signal for MMP-9 messenger RNA. Wound fluid contained mainly MMP-9, the amount of which was highest in two- to four-day-old secretions. None of the cytokines tested (transforming growth factor beta-1, interleukin-1 beta, basic fibroblast growth factor, tumor necrosis factor-alpha, interferon-gamma) were able to regulate MMP-2 expression in cultured wound fibroblasts. However, keratinocyte MMP-9 production was enhanced by interleukin-1 beta, transforming growth factor beta-1, and tumor necrosis factor-alpha. CONCLUSIONS: During wound healing, MMP-9 is suggested to be involved in keratinocyte migration and granulation tissue remodelling. Expression of MMP-2 remains stable during wound healing.

Cells, Cultured↗

PubMed1994

Diffuse renal disease. Diagnosis by ultrasound-guided cutting needle biopsy.

The results of ultrasound (US)-guided renal parenchymal cutting needle biopsies in 101 consecutive patients were reviewed. The biopsies were done with the automated Biopty device mounted with a 2.0-mm needle. One or 2 needle passes yielded sufficient material for histologic analysis in 94% (95/101). Three or more passes were required in 6% (6/101) to obtain an adequate specimen. Mesangioproliferative glomerulonephritis, IgA-nephropathy, nephrosclerosis, diabetic nephropathy, secondary amyloidosis, lupus nephritis, minimal change glomerulonephritis and interstitial nephritis accounted for 79% of the final histologic diagnoses. The high quality and quantity of the tissue specimens yielded a definitive histologic diagnosis in renal parenchymal diseases of unknown etiology. Four major complications occurred, but no deaths or loss of kidney function were recorded. US proved useful as a guide to suitable biopsy site and in the detection of clinically significant complications. Prebiopsy screening of coagulation variables did not seem to prevent complications. Special attention should be paid to post-biopsy clinical observation.

Adolescent↗

PubMed1993

Evaluation of PAP and PSA gene expression in prostatic hyperplasia and prostatic carcinoma using northern-blot analyses, in situ hybridization and immunohistochemical stainings with monoclonal and bispecific antibodies.

In this report we have investigated levels of prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) gene expression in prostatic carcinoma (Ca) and benign prostatic hyperplasia (BPH) specimens. Northern-blot analyses of total prostatic mRNA indicated that there was a tendency towards lower amounts of PAP mRNA and PSA mRNA in the Ca specimens than in the BPH specimens, although, because of the great variation in the expression levels of both mRNAs, these differences were not statistically significant. In situ hybridization analyses clearly showed that both PAP and PSA mRNAs were confined to the columnar epithelial cells and that stromal cells were devoid of these mRNAs. In addition, PAP and PSA mRNAs were more abundant in BPH tissue than in adjacent Ca tissue within the same specimen. The levels of PAP and PSA enzymes were analyzed immunohistochemically using a bispecific antibody having high affinity for both PAP and PSA, and the results were compared with those obtained using monoclonal anti-PAP and anti-PSA antibodies. All 3 antibodies stained only epithelial cells and BPH tissue consistently gave more intense staining than Ca tissue. Furthermore, the anti-PSA and the bispecific anti-PAP-PSA antibodies stained well or moderately differentiated Ca tissues more strongly than poorly differentiated Ca tissues. No PSA staining was detected in 3 and no PAP staining in 5 of the moderately or poorly differentiated carcinomas (grades II or III). Our results show that, in comparison with BPH tissue, prostatic Ca tissue is associated with significantly lower levels of mRNAs coding for the prostatic marker enzymes PAP and PSA, as well as with lower concentrations of these enzymes. Furthermore, dedifferentiation of prostate Ca is associated with a decrease in the level of intraprostatic PSA.

Acid Phosphatase↗

PubMed1993

Synthesis and degradation of basement membranes in benign and malignant salivary gland tumours. A study by in situ hybridization.

In this study we investigated the mRNA expressions of 72 kD and 92 kD type IV collagenases, alpha 1(IV) chain of type IV collagen, and laminin B1 chain mRNAs in a set of malignant and benign salivary gland tumours and compared the results with non-neoplastic salivary gland tissue. While only a few cases expressed 72 kD type IV collagenase mRNA or alpha 1(IV) chain of type IV collagen mRNA in tumour cells, 92 kD type IV collagenase and laminin mRNA synthesis could be seen in the neoplastic cells of many tumours. Stromal fibroblasts or endothelial cells demonstrated mRNA synthesis for all these proteins to a variable degree except for Warthin's tumours, in which no synthetic activity for any of the proteins could be seen. Since signals for 92 kD type IV collagenase mRNA could be seen in non-neoplastic epithelial cells of the salivary gland, the synthesis of 92 kD type IV collagenase by tumour cells can be regarded as an intrinsic property of salivary gland epithelial cells. The pattern of mRNA synthesis for 72 kD and 92 kD type IV collagenases follows that observed in other tumours, in which the stromal cells also mainly synthesize 72 kD type IV collagenase while epithelial tumour cells more readily express 92 kD type IV collagenase mRNA. The synthesis of type IV collagenases by malignant tumours has been suggested to be of crucial importance for invasion and metastasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenolymphoma↗

PubMed1993

p53 immunohistochemistry in transitional cell carcinoma and dysplasia of the urinary bladder correlates with disease progression.

Immunohistochemically detectable p53 protein using a polyclonal antibody (CM-1) was studied in 42 carcinomas of which 11 were grade I, 22 grade II and nine grade III carcinomas. Additionally 14 urothelial dysplasias were studied. In 11 of these a diagnosis of transitional cell carcinoma was established before and in one after the dysplasia diagnosis. Twenty-one out of 42 (50%) cases of transitional cell carcinoma were positive for the p53 protein. Eleven out of 14 (78%) dysplasias and 10/12 (83%) related carcinomas were p53 positive. One out of 11 grade I (9%), 12/22 grade II (55%) and 8/9 grade III (89%) tumours showed positivity for p53. There were significantly more p53 positive cases in grade II-III tumours than in grade I tumours (P = 0.004). There were significantly more p53 positive cases in stage T2-T4 tumours than in stage T1 tumours (P = 0.035). In only one case among the 11 dysplastic lesions following the treatment of a carcinoma the dysplastic lesion was p53 negative while the preceding carcinoma was p53 positive. All dysplasias and 28 carcinomas were also immunostained for laminin and type IV collagen to evaluate the continuity of basement membranes (BMs). Clearly disrupted BMs were observed only in grade III carcinomas. These cases showed the most p53 immunopositivity. The results show a strong association of p53 staining between dysplasias and transitional cell carcinomas of the urinary bladder indicating that these lesions might share similar p53 changes. The correlation to grade, clinical stage and to disrupted BM suggests that p53 mutations may be associated with the evolution of aggressive growth characteristics in transitional cell carcinomas or, alternatively, that p53 positive tumours of a more aggressive type from the start. Whether p53 staining can be used as an adjunct in the assessment and follow-up of epithelial changes of patients treated for a p53 positive bladder carcinoma deserves to be studied.

Carcinoma, Transitional Cell↗

PubMed1993

Demonstration of 72-kDa and 92-kDa forms of type IV collagenase in human skin: variable expression in various blistering diseases, induction during re-epithelialization, and decrease by topical glucocorticoids.

Type IV collagenases have been shown to play an important role in tumor metastasis and wound healing. In the present study, we have demonstrated the presence of 72-kDa and 92-kDa forms of type IV collagenase in human skin by biochemical and in situ hybridization techniques. In situ hybridization allowed us to localize the 72-kDa form mostly to fibroblasts and the 92-kDa form to the epidermis and endothelial cells. The presence of type IV collagenase was confirmed by Western blotting. Enzyme activity was assayed in spontaneous blisters (18 subjects) and suction-induced blisters (29 subjects) by the zymography method, and by using type IV collagen as the substrate. Thus, it was possible to detect both the 92-kDa and 72-kDa forms in spontaneous and induced blisters. An especially high level of the 92-kDa enzyme was found in a bullous pemphigoid patient. Type IV collagenases were studied during re-epithelialization of the blister, using the suction-blister model. There was a marked induction of the 92-kDa type that was confirmed to be in the regenerating, migratory, epithelium by in situ hybridization studies. These results indicate that 92-kDa type IV collagenase may play an essential role in the normal physiology and integrity of the skin and may be an important regulator of re-epithelialization. It was also shown that potent topical glucocorticoid down-regulated the 92-kDa type collagenase, suggesting that glucocorticoids may have a beneficial role in some skin diseases by decreasing type IV collagenase activity and, thus, reducing tissue destruction.

Administration, Topical↗

PubMed1993

Location and alternative splicing of type XIII collagen RNA in the early human placenta.

BACKGROUND: Type XIII collagen is widely distributed in the fetus. It is characterized by complex alternative splicing of its primary transcripts in regions corresponding to nine exons of the gene. EXPERIMENTAL DESIGN: Localization of type XIII collagen mRNAs in early placentas was determined by in situ hybridization. Reverse-transcription-polymerase chain reactions were used to examine alternative splicing of nine exons in villous and decidual mRNAs. RESULTS: An intense in situ hybridization signal was observed in the fibroblastoid stromal cells of the placental villi. A moderate signal was found in the endothelial cells of developing capillaries and the cells of the cytotrophoblastic columns. Furthermore, mRNAs were detected in the large decidual cells of the decidual membrane and the stromal cells of the gestational endometrium, but not in the epithelial cells in the endometrial glands. Five combinations of exons 3B, 4A, 4B and 5, encoding half of the COL1 domain, were found. The combination lacking exons 3B-5 was the major variant in both villous and decidual mRNAs. Three combinations of exons 12 and 13 encoding the NC2 domain were found, the long variant containing either 12 or 13 sequences being the major variant in the villi while nearly equal amounts of long and short variants lacking both 12 and 13 sequences were observed in the decidua. Four variants of exons 29, 33 and 37, encoding parts of COL3 and NC4, were found as splicing out of exon 37 was not detected. The major variants in both mRNAs were two that lacked exon 29 and either lacked or contained exon 33 sequences. CONCLUSIONS: Type XIII collagen mRNAs were located in the placenta. Due to alternative splicing, the lengths of the COL1 and NC2 domains of this collagen vary from 57 to 104 and from 12 to 34 amino acids, respectively. The COL3 domain varies between 208 and 235 residues, whereas the NC4 is 18 residues.

Base Sequence↗

PubMed1993

Expression of 72 kilodalton type IV collagenase (gelatinase A) in benign and malignant ovarian tumors.

BACKGROUND: 72 Kilodalton (kd) type IV collagenase is a matrix metalloproteinase that specifically cleaves type IV collagen molecules. The enzyme has been postulated to have an important role in the invasion and spread of malignant tumors. EXPERIMENTAL DESIGN: In situ hybridization was used to study the expression of the 72 kd type IV collagenase mRNA in 24 benign, 2 semimalignant, and 15 malignant ovarian tumors and in 5 metastases of ovarian serous adenocarcinomas. The results were correlated with the expression of the mRNA for the alpha 1(IV) chain of type IV collagen and with the corresponding immunohistochemical distribution of the enzyme. RESULTS: The results showed that the more malignant an ovarian tumor was, the more clearly mRNA expressions for both 72 kd type IV collagenase and the alpha 1(IV) chain could be detected in tumor cells. The expression of both types of mRNAs was localized within the cells of tumor stroma and occurred mainly in fibroblasts and vascular endothelial cells. Epithelial tumor cells only rarely expressed these mRNAs. Immunohistochemical stainings localized the 72 kd collagenase as well to the stromal cells as to the epithelial cells of both benign and malignant tumors. CONCLUSIONS: The findings indicate that genes for the 72 kd type IV collagenase and for its substrate are simultaneously active in the same cells of the tumor stroma. The difference in the in situ hybridization and immunohistochemical findings could be explained by a possible variation in the metabolic balance between synthesis and accumulation of the protein in different cell types. It can also be proposed that the activity of the 72 kd type IV collagenase would be mediated through a receptor-like mechanism present on epithelial cells which could bind the 72 kd type IV collagenase synthesized elsewhere. There is also a possibility that the gelatinolytic activity of the mesenchymally synthesized 72 kd type IV collagenase would be consumed to degrade extracellular matrix proteins other than basement membranes.

Adenocarcinoma↗

PubMed1993

Expression of 72 kilodalton and 92 kilodalton type IV collagenase in malignant fibrous histiocytomas and dermatofibromas.

BACKGROUND: In previous studies, it has been shown that the stromal cells of epithelial tumors are capable of synthesizing 72 and 92 kilodalton (kd) type IV collagenase mRNA. The mRNA synthesis of these collagenases in mesenchymal tumors has not been extensively studied, however. This study was undertaken to explore the synthesis of 72 and 92 kd type IV collagenase mRNAs in malignant and benign fibrous histiocytomas and its correlation with the known biologic behavior of these tumors. EXPERIMENTAL DESIGN: The synthesis of 72 kd and 92 kd type IV collagenase mRNA was studied in 10 malignant fibrous histiocytomas (MFHs) and 7 dermatofibromas using in situ hybridization methods. The tumors were also studied with a commercial monoclonal antibody to the 72 kd type IV collagenase. Additionally, three dermatofibromas were studied with an antibody to the 92 kd type IV collagenase. The media of three cell lines (MFH, dermatofibroma and skin fibroblast cell line) were also analyzed by zymography assay. RESULTS: The results revealed mRNA for the 72 kd and 92 kd collagenases in tumor cells of both MFHs and dermatofibromas. Also intracytoplasmic immunoreactivity for the 72 kd type IV collagenase could be seen in all the tumors. In the zymography assay, 72 kd type IV collagenase activity was detected in the culture media of all the cell lines tested, but activity for the 92 kd enzyme was only seen in the MFH. However, immunoreactivity for the antibody to the 92 kd type IV collagenase was also seen in dermatofibromas. CONCLUSIONS: The findings indicate that MFHs and dermatofibromas produce type IV collagenases. The synthesis of the mRNAs for both 72 kd and 92 kd type IV collagenase was quantitatively similar in MFHs and dermatofibromas indicating that there is no correlation between the biologic behavior of the tumors and the synthesis of these substances. Therefore, additional factors other than synthesis of type IV collagenases by tumor cells, must be involved in the process of spread and invasion of tumor cells into the neighbouring tissues.

Aged↗