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At least 505 records · Page 28Linked to original sources
PubMed1994

Can tenascin be redundant in cancer development?

Histological and biochemical analyses of tenascin in various human tumors have indicated that tenascin is expressed in various cancer stroma and increased in the serum, getting strong with advancement of its malignancy. Of interest, the prognostic analysis of breast and colon cancers revealed favorable survival and no lymphogenous metastasis in patients whose cancer expressed tenascin strongly. Injection of tenascin nonproducing A431 human epidermoid cancer cells into nude mice resulted in tenascin production by these cells, suggesting cancer cells can make tenascin if necessary. Thus, both carcinoma and adjacent stroma cells may produce tenascin to coordinate the microenvironment surrounding the cancer tissues. Several tenascin variants have been clearly demonstrated to date. With these findings in mind, we would propose that epithelial tenascin supports the carcinoma cell outgrowth, whereas stromal tenascin may block cancer invasion by covering the cancer nest. No obvious phenotype in tenascin gene knockout mice would indicate that tenascin is functionally redundant in developmental processes, yet it may well be very important in progression of cancer.

Animals↗
PubMed1995

Human/mouse radiation chimera are capable of mounting a human primary humoral response.

Lubin et al recently described a new approach that enables the generation of human/mouse chimera by adoptive transfer of human peripheral blood mononuclear cells (PBMC) into lethally irradiated normal strains of mice, radioprotected with bone marrow (BM) from donors with severe combined immune deficiency (SCID). In the present study, we demonstrate in such human/mouse chimera a marked humoral response to recall antigen, such as tetanus toxoid (TT) or hepatitis B surface antigen (HBsAg), as well as a significant primary response to keyhole limpet hemocyanin (KLH). Maximal anti-KLH response in human/Balb chimera was attained 2 to 4 weeks after the immunization and declined thereafter. One week after transplantation, the predominant anti-KLH subtype was IgM, while after 2 weeks, the dominance had shifted to IgG. Similar primary antibody response was also demonstrated against the human immunodeficiency virus (HIV) Nef protein. Comparison between human/Balb and human/SCID chimera showed a major difference in their ability to mount a primary response against KLH. In Balb/c recipients, more than half of the mice exhibited marked IgM titers against KLH, while there was hardly any anti-KLH IgM response in the SCID recipients. From the earliest time point onwards, when anti-KLH antibodies were found in the latter chimera, they were predominantly of the IgG type. We have previously shown that in human/Balb chimera, unlike in SCID recipients, dissemination of transplanted PBMC into the spleen and other internal organs occurs within 24 hours. Therefore, it is likely that the early seeding in the appropriate microenvironment of the lymphoid tissues, is crucial for the maintenance of virgin human B cells.

Animals↗
PubMed2001

[Tumor escaping mechanisms present in microenvironment of laryngeal cancer].

In tumor tissue obtained from a group of 21 patients treated surgically for laryngeal carcinoma, the expression of Fas, Fas-L, CD3, TCR zeta chain and Bcl-2 were estimated. It has been shown that tumor often express: Fas-L, Fas, Bcl-2, the molecules which may influence increased tumor survival. On the other hand lack of MHC class I antigen expression on tumor cells frequently has been observed. As it is known, such tumor cells can not be recognized by cytotoxic T lymphocytes. Frequently observed decreased expression of TCR zeta chain and high level of apoptosis among T cells present in tumor microenvironment seems to depend on direct interactions with molecules expressed by tumor. Understanding of these interactions may be of great importance in evaluation of tumor aggressiveness, patients follow up and the approach to treatment.

Adult↗
PubMed2004

Cografting of hamster (Phodopus sungorus) and marmoset (Callithrix jacchus) testicular tissues into nude mice does not overcome blockade of early spermatogenic differentiation in primate grafts.

The ectopic xenotransplantation of testicular tissues into nude mice is a tool to generate sperm from immature testes. Immunodeficient mice as recipients of xenografts offered an appropriate microenvironment for differentiation of testicular tissue from hamsters, goats, pigs, and macaques. One exception is the neotropical primate Callithrix jacchus. Spermatogenesis in testicular grafts from marmosets does not proceed beyond the spermatogonial stage. The most likely cause for the poor graft development of marmosets is a deletion of exon 10 in the luteinizing hormone-receptor (LHR) gene, which renders this species insensitive to LH but responsive to chorionic gonadotropin (CG). We investigated whether cografting of testicular tissue from Djungarian hamsters would overcome the blockade in marmoset graft development. We also tested if exogenous administration of human CG (hCG) to the recipient would stimulate development of the marmoset tissue. No difference in graft survival was noted between hamster and monkey tissue. Seminiferous lumina were present in marmoset and hamster grafts but were significantly larger in hamster grafts. In the hamster grafts, a high proportion of the tubules contained meiotic and postmeiotic germ cells. In contrast, the marmoset tubules were populated with gonocytes and premeiotic spermatogonia. These results indicate that neither normal serum androgen levels nor the high local testosterone levels were sufficient to initiate marmoset spermatogenesis, nor was administration of hCG successful in overcoming the developmental blockade in marmoset tissue. Our results indicate that the conditions needed for initiation of spermatogenesis in the marmoset are remarkably different from those present in most other mammals.

Androgens↗
PubMedDate not supplied

Role of the host microenvironment on the expression of VEGF-subtypes in squamous cell carcinoma.

The phenotypic characteristics and function of microvascular endothelium differs from tissue to tissue because of the organ specific microenvironment. Even the neovasculature in tumors differs depending upon tumor location. These findings indicate that local regulatory pathways modulate endothelial-cell growth and -function in a tissue specific manner. This might be mediated by novel tissue-specific regulators or the tissue specific regulation of known proteins. One of the major proangiogenic factors is VEGF. Its importance for tumor vascularisation and growth has been shown in several studies. VEGF is expressed in several subtypes and its impact on initial tumor growth and tumor progression has been discussed. Many of these results have been obtained by xenotransplantation studies in mice. The influence of the mouse microenvironment on the VEGF-subtype expression has not been previously analyzed. In the present study we analyzed the impact of the nude mouse microenvironment on the expression of the VEGF-subtypes after subcutaneous xenotransplantation. Our study was performed on seven squamous cell carcinoma (SCC) cell lines. We analyzed by quantitative PCR the mRNA-expression levels and the proportion of the subtypes -121, -165, -189, and of VEGF-total of established xenotransplanted tumors and compared them to the cell lines prior to transplantation. We found high VEGF-165 fractions in the cell lines leading to fast growing, large tumors. The proportion of the VEGF-isoforms remaining in the cell lines and xenotransplanted tumors were generally unchanged, but an overall decrease of VEGF by about 50% was observed. We conclude that the VEGF-subtypes expressed by the transplanted tumors are not differentially regulated by the nude mouse subcutaneous microenvironment and that the tumor growth characteristics are not dependent on VEGF-subtype regulation of the host.

Animals↗
PubMed1998

Differential distribution of Fc gamma RIIIa in normal human tissues and co-localization with DAF and fibrillin-1: implications for immunological microenvironments.

Fc gamma RIIIa is a cytokine-inducible IgG Fc receptor implicated in the activation of macrophages by immune complexes. Differential expression of Fc gamma RIIIa by macrophages in different tissues may therefore modulate local immune responsiveness. Fc gamma RIIIa expression in normal human tissues was assessed semiquantitatively using microdensitometry. Synovial intimal, serosal, alveolar, salivary gland and placental macrophages, Kupffer cells, and macrophages in mechanically stressed dermis expressed high levels of Fc gamma RIIIa. Less consistent expression was seen in skeletal muscle and lymphoid organs. No significant expression was observed in brain, thyroid, spine, intestine, myocardium, prostate, uterus, flexor forearm dermis, uterus, or kidney. Staining for Fc gamma RIII was also observed on extracellular matrix, and co-localized with both complement decay-accelerating factor and fibrillin-1. It is proposed that differential levels of both cellular and extracellular Fc gamma RIIIa, by modulating the response to immune complexes, may contribute to relative tissue susceptibility to infection and autoimmune disease.

CD55 Antigens↗
PubMed2006

Heterologous protein production capacity of mammalian cells cultivated as monolayers and microtissues.

A precise understanding of processes managing heterologous protein production in vitro and in vivo is essential for the manufacture of sophisticated biopharmaceuticals as well as for future gene therapy and tissue engineering initiatives. Capitalizing on the gravity-enforced self-assembly of monodispersed cells into coherent (multicellular) microtissues we studied heterologous protein production of microtissues and monolayers derived from cell lines and primary cells engineered/transduced for (i) constitutive, (ii) proliferation-controlled, (iii) macrolide-, or (iv) gas-inducible expression of the human placental secreted alkaline phosphatase (SEAP) and of the Bacillus stearothermophilus-derived secreted alpha-amylase (SAMY). Specific productivity of cells assembled in microtissues was up to 20-fold higher than isogenic monolayer cultures. Diffusion across microtissues could be further increased by HUVEC-mediated vascularization. As well as higher specific protein productivities, microtissues were also more efficient than monolayer cultures in assembling transgenic lentiviral particles. Our results showed that mammalian cells embedded in a tissue-like three-dimensional (3D) microenvironment exhibit increased production capacity. This observation should be considered for gene therapy and tissue engineering scenarios as well as for biopharmaceutical manufacturing.

Alkaline Phosphatase↗
PubMed1996

Dendritic cells from different tissues induce production of different T cell cytokine profiles.

The precise role of antigen-presenting cells (APC) in regulating the balance of T-helper type 1 (Th1) and T-helper type 2 (Th2) cytokine production is unclear. Dendritic cells (DC), the most potent APC for activation of naive T cells, were found to regulate Th1 and Th2 cytokine profiles in a fashion dependent upon their tissue of origin. Spleen (systemic) DC induce mainly Th1 cytokines and Peyer's patch (mucosal) DC induce predominantly Th2 cytokines. These findings support the current concept that different tissues, each with its distinct microenvironment of cytokines, hormones, and cellular elements, are involved in the selection, promotion, and/or maintenance of different immune responses. With regard to DC, it is apparent that the tissue of DC origin determines the cytokine profiles produced by T cells and that DC from different tissues favor either cellular versus humoral immune responses by influencing T cell cytokine production.

Animals↗
PubMed1992

The renewal and differentiation of hemopoietic stem cells.

Blood-forming tissues are organized in well-defined microenvironments composed of hemopoietic cells and a supportive stroma of connective tissue and endothelium. Hemopoietic cells segregate to various lineages, all derived from a small population of pluripotent stem cells residing in the bone marrow. Regulation of growth and differentiation, particularly under conditions of perturbations, damage, and disease, is mediated by inducer colony-stimulating factors and interleukins counteracted by inhibitory cytokines. Whereas much is known about the mode of induction of differentiation, insufficient information is available to explain the process of stem cell renewal that is crucial for the longevity of the hemopoietic system. It is also only partially known how inhibition of hemopoietic processes occurs, and what molecules in blood-forming tissues signal organization into discrete patterns. This paper reviews recent progress that has opened new avenues to a better understanding of this highly complex issue.

Animals↗
PubMed2004

Three-dimensional in vitro tissue culture models of breast cancer-- a review.

Three-dimensional (3D) in vitro breast tumour models have an invaluable role in tumour biology today providing some very important insights into breast cancer. As well as increasing our understanding of homeostasis, cellular differentiation and tissue organization they provide a well defined environment for cancer research in contrast to the complex host environment of an in vivo model. With the recent availability of relevant stromal elements together with the vast array of extracellular matrix constituents available, in vivo like microenvironments can be recreated. These tissue like structures more realistically model the structural architecture and differentiated function of breast cancer than a cellular monolayer providing in vivo like responses to therapeutic agents. Three dimensional in vitro models allow the study of cell-cell and cell-extracellular matrix interactions, in addition to the influence of the microenvironment on cellular differentiation, proliferation, apoptosis and gene expression. Due to their enormous potential 3D cultures are currently being exploited by many other branches of biomedical science with therapeutically orientated studies becoming the major focus of research. In return great progress in 3D culture techniques have been made, largely due to this greater interaction. At present they are being used in studies ranging from investigating the role of adhesion molecules (e.g., E-cadherin) in invasion/metastasis; VEGF and angiogenesis, to tissue modelling and remodelling. Progress in the development of complex 3D culture systems is more productive than ever, however further research is vital.

Breast Neoplasms↗
PubMed1984

Connective tissue elements in rat bone marrow: immunofluorescent visualization of the hematopoietic microenvironment.

Immunofluorescent staining of frozen sections of rat bone marrow for collagen types I and III revealed the presence of a distinctive, collagen-producing cell type. Morphologically, these cells closely resembled reticular cells. They were large, with branching cytoplasm and were closely related to an extensive intercellular matrix of collagenous material that surrounded the hematopoietic cells of the marrow. Biochemical studies demonstrated synthesis of collagen types I and III, in a ratio of 4:1, by fresh rat bone marrow cells.

Animals↗
PubMed2004

Tropheryma whipplei Infection of an acellular porcine heart valve bioprosthesis in a patient who did not have intestinal Whipple's disease.

Rare cases of culture-negative infective endocarditis are caused by Tropheryma whipplei, the uncommon bacterium of Whipple's disease. We evaluated an 80-year-old woman with valvular heart disease but without intestinal Whipple's disease. The diagnosis of aortic valve xenograft culture-negative infection with T. whipplei was established by multiple molecular assays and by electron microscopy. First, a PCR with broad-range primers identified the complete 16S ribosomal DNA of T. whipplei in bioprosthesis tissue. Novel real-time reverse transcription-PCR assays were developed to detect mRNAs encoding recently identified proteins determined from the T. whipplei genome, specifically Whipplei surface protein (TW113) and a DNA polymerase III subunit (TW727). The positive detection of mRNAs indicated the presence of metabolically active bacteria and suggested the viability of T. whipplei. The quantification of T. whipplei genome equivalents by real-time PCR indicated a high-density bacterial colonization of the valve tissue. Additionally, an ultrastructural examination revealed numerous rod-shaped bacteria consistent in size with T. whipplei in the extracellular collagen matrix of the bioprosthesis. We conclude that extracellular growth of T. whipplei can occur in the microenvironment of biological prosthetic valve tissue and that T. whipplei endocarditis can occur in the absence of intestinal Whipple's disease.

Actinomycetales↗
PubMed2006

Oncostatin m maintains the hematopoietic microenvironment and retains hematopoietic progenitors in the bone marrow.

Bone marrow (BM) functions as the primary hematopoietic tissue throughout adult life by providing a microenvironment for the proliferation, differentiation, and retention of hematopoietic stem cells and progenitors. We describe novel roles for oncostatin M (OSM) in the BM hematopoietic microenvironment. Hematopoietic progenitor activity in OSM-deficient mice was reduced in BM but elevated in the spleen and peripheral blood. The level of circulating granulocyte colony-stimulating factor (G-CSF) was increased, whereas that of stromal cell-derived factor 1 (SDF-1) was decreased in OSM-deficient mice. Moreover, the ability of OSM-deficient BM stromal cells to support hematopoiesis in vitro was significantly reduced. These results indicate that OSM plays a unique role in hematopoiesis by maintaining the proper microenvironment for BM hematopoiesis; it also retains hematopoietic progenitors in BM by regulating G-CSF and SDF-1 levels.

Animals↗
PubMed1990

Spinal cord repair: is tissue oxygenation an important variable?

We have demonstrated the reliability and feasibility of making PtO2 recordings from graft and host tissue in the injured spinal cord. The data suggest that the oxygen microenvironment of developing graft and host spinal tissue is clearly different from that found in normal spinal tissue or in transplants that have not survived or integrated well. These same constraints seem to apply to cavitation in developing grafts and poorly developed graft/host interfaces. The similarity between these findings and those from previous studies in other fetal vertebrates suggests that oxygen tensions in the spinal cord probably reflect the developmental status of the regenerating tissue. Our future studies will seek to define the relationship between anatomical development of transplant tissue and these functional (PtO2, microvascular development and tissue metabolism) indicators of graft development. These investigations should also provide a background for those later studies which seek to establish the mechanisms by which these relationships come about i.e. oxygen consumption of host/transplant tissue, blood flow to transplants, studies of glycolytic metabolism (2-DG autoradiography), etc. In this way, we can begin to understand the role of tissue metabolism in graft-mediated repair.

Animals↗
PubMed2006

Membrane-associated TGF-beta1 inhibits human memory T cell signaling in malignant and nonmalignant inflammatory microenvironments.

TGF-beta1 is present on cells derived from the microenvironment of human lung tumors and nonmalignant inflammatory tissues. We establish that this cell-associated cytokine mediates hyporesponsiveness of the memory T cells in these microenvironments in situ by blocking TCR signaling. T cells derived from these tissues failed to translocate NF-kappaB to the nucleus in response to CD3 + CD28 cross-linking. This nonresponsiveness was reversed by an anti-TGF-beta1-neutralizing Ab. Refractoriness of the memory T cells to TCR activation was also reversed by the removal of TGF-beta1 by briefly pulsing the cells in a low pH buffer. Addition of exogenous TGF-beta1 to eluted T cells re-established their nonresponsive state. Neither TGF-beta1, anti-TGF-beta1 Ab, nor low pH affected TCR signaling potential of peripheral blood T cells. We conclude that TGF-beta1 mediates a physiologically relevant regulatory mechanism, selective for memory T cells present in the tumor microenvironment and nonmalignant chronic inflammatory tissues.

Antibodies↗
PubMed1991

[Regeneration of bone marrow tissue. Growth and differentiation of hematopoietic stem cells and the role of bone marrow microenvironment on hematopoiesis].

Hematopoietic stem cell proliferation and differentiation is regulated by a multistep process involving stem cell self-renewal, commitment, differentiation and maturation. Each process is controlled by a variety of humoral factors and cell-cell interactions, i.e., (i) growth factor and growth inhibitor acting toward the cascade of stem cell proliferation and differentiation, (ii) cytokine network involving cytokine-producing hematopoietic cells and stromal cells, (iii) interaction between hematopoietic cells and bone marrow microenvironment that is consisted of stromal cells and extracellular matrix. Recent advances in cell biology and cell physiology enabled us to understand the roles of these marrow microenvironments on hematopoiesis in molecular basis. We here discuss the complexities of hematopoietic system and the mechanism of the regeneration of hematopoietic tissues in special reference to bone marrow transplantation.

Animals↗
PubMed2006

Fabrication methods of an engineered microenvironment for analysis of cell-biomaterial interactions.

Success in tissue engineering requires an understanding of how cells integrate the signals presented from the microenvironment created by biomaterial scaffolds to alter their responses. Besides the presence of chemical stimuli, there is growing evidence that the spatial organization of cells and tissue within a 3-dimensional (3-D) extracellular matrix (ECM) context is a critical element in controlling cellular function. Therefore, in order to direct cells toward a desirable tissue structure, it is necessary to engineer biomaterials to have spatiotemporal control of the presentation of regulatory signals. Given that, micro-patterning techniques have profited by combining micro-fabrication technology with the chemical conjugation of biologically active molecules to provide new culture systems where cells can be cultured within a specific geometry. The micro-engineered environments have been developed as 2- and 3-D structures, which have proven greatly useful as versatile platforms to study cell, biomaterial, and ECM interactions on both macroscopic and microscopic levels. The main focus of this review is a brief summary of the use of micro-engineered substrates in the analysis of cell-biomaterial interactions with the aim to provide an introductory overview of practical applications available in the literature. In particular, topics regarding (1) the soft-lithography technique to prepare micro-patterned substrates for the spatial control of cell adhesion, (2) biomaterials stiffness-dependent cellular responses, and (3) the microarray techniques for analysis of cell/biomaterials interactions are discussed.

Animals↗