Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tenascin is an extracellular matrix glycoprotein produced in response to epithelial-mesenchymal interactions that initiate fetal organogenesis, and it is also found in the stroma of benign and malignant neoplasms. Thirty-five human cell lines representing a variety of cancers were examined by immunoprecipitation and polyacrylamide gel electrophoresis of radiolabeled tenascin proteins from conditioned media. Two forms of tenascin with relative molecular masses of 190,000 and 250,000 were identified. Eight cell lines produced both forms. With the exception of myeloid and lymphoid leukemias and Burkitt's lymphoma, all of the mesodermal and neuroectodermal tumor lines were found to synthesize tenascin. Unexpectedly, tenascin was secreted by several mammary and colonic adenocarcinomas as well as by a line derived from normal mammary epithelial cells, and in some cases increased production was induced by transforming growth factor beta in serum-free medium. Cells producing fibronectin but not tenascin attached and spread on plastic culture dishes, while those producing tenascin alone remained suspended in the medium or were rarely attached. Tenascin also inhibited fibronectin-mediated adhesion of MCF7 breast carcinoma cells in vitro. The results suggest that tenascins synthesized and secreted by some cancer cells, especially those of epithelial origin, may have specific roles in determining tumor cell adhesion and ultimately the ability to form invasive outgrowths.
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PMID:Human carcinoma cells synthesize and secrete tenascin in vitro. 128 Jun 34

We investigated the expression of beta 1 integrins in human carcinoma cell lines, and the anti-metastatic and anti-invasive effects of a newly established anti-human beta 1 subunit monoclonal antibody designated NCC-INT-7. All the examined carcinoma cell lines expressed beta 1 integrins upon immunoblot analysis. NCC-INT-7 completely inhibited the adhesion of carcinoma cells to laminin, fibronectin, collagens and acetone-fixed tissues including lung, liver and brain. In an in vitro invasion model, NCC-INT-7 inhibited the invasion of human bladder carcinoma cell line T24 and human gastric carcinoma cell lines TMK-1, MKN-45 and MKN-74 through an artificially reconstructed basement membrane. In an in vivo nude mouse peritoneal dissemination model using MKN-45 and TMK-1, NCC-INT-7 significantly reduced the number of tumor nodules in the mesentery. In an in vivo nude mouse liver metastasis model using a serially transplantable human colonic carcinoma, COL-2-JCK, NCC-INT-7 significantly reduced the number of tumor nodules in liver. These results indicate that beta 1 integrins play an important role in the tissue attachment, migration, invasion and metastasis of human carcinoma cells, and that this new monoclonal antibody is useful for studies aimed at prevention of metastasis.
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PMID:Inhibition of cell attachment, invasion and metastasis of human carcinoma cells by anti-integrin beta 1 subunit antibody. 128 8

Regulation of a number of adhesion molecules during neural crest cell migration was studied. The neural crest, a transient embryonic neural epithelium structure, undergoes mesenchymal transformation (epithelial-mesenchymal transition). The cells then migrate, giving rise to a variety of elements including the peripheral nervous system and melanocytes. During migration, neural crest cells do not express functional cell Adhesion Molecules but interact specifically with cell-binding domains in fibronectin molecules. A rat bladder carcinoma cell line was used as an in vitro model to study conversion of epithelial cells to a migratory fibroblast-like state. Conversion can be induced by culture on collagen or exposure to acidic Fibroblast Growth Factor (aFGF). Furthermore, constitutive fibroblast-like transformation can be induced by transfection with cDNA encoding aFGF. Growth factor-producing clones exhibit increased invasive and metastatic properties as compared with non-FGF-producing control cells. This model may provide increased understanding of the role of the different adhesion molecules in processes involving cell remodeling, such as tumor spread and development of metastases.
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PMID:[Adhesion and mobility of embryonic and tumoral cells]. 128 12

In tumor progression, populations of cancer cells with different patterns of growth and invasion arise within the same tissue and within individual neoplasms. We tested the hypothesis that, even in histologically undifferentiated carcinomas, such diversity may be influenced by differentiation-dependent adhesive mechanisms. We used as prototypes two cell lines that originated in the same clone of a poorly differentiated cervical carcinoma, but express strikingly different phenotypes. Cells of line C-4I express select characteristics of the spinous stage of stratified squamous epithelial differentiation while cells of line C-4II resemble basal cells. C-4I cells form rapidly expanding compact tumors in vivo and multilayered cohesive colonies in culture, while C-4II cells form slow-growing infiltrating tumors in vivo and dispersed, monolayered colonies in culture. In suspension culture which prevented any cell-substratum interactions, C-4I cells formed aggregates that were significantly larger and more compact than those formed by C-4II. Thus, greater intercellular adhesion between the 'spinous' C-4I cells contributed significantly to the phenotypic divergence of the lines. Upon disruption of intercellular adhesion with the glutamine analogue 6-diazo-4-oxo-norleucine (DON), C-4I cultures on plastic and in suspension assumed forms resembling C-4II. On plastic, single 'basal' C-4II cells adhered more rapidly and migrated more slowly than C-4I cells, in keeping with the capacity of C-4II, but not C-4I, to secrete fibronectin (FN) substrata. However, on exogenous FN matrices, migration and cell dispersion were accelerated in both lines. Both lines expressed similar integrin profiles. Thus, the lines had diverged in extracellular matrix production, but not in the receptors for extracellular matrix components. The properties of the C-4 lines mimic those of specific cell types in normal stratified squamous epithelia, where intercellular adhesion increases but FN secretion diminishes with progression from the basal to the spinous stage of differentiation. Our results demonstrate a direct influence of differentiation-associated adhesive mechanisms on growth patterns and suggest that similar mechanisms may be responsible for variations in invasiveness among neoplastic clonal subpopulations. An awareness of these correlations may help to interpret the modes of local invasion by poorly differentiated carcinomas in terms of specific, well-defined cell properties.
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PMID:Divergence in patterns of invasion among subpopulations derived from a human carcinoma clone: roles of intercellular contacts and of cell-substratum adhesion. 129 33

The invasiveness of human gastric carcinoma cell lines (MKN45 and MKN28) in the subcutaneous tissue of nude mice and the degrading capacities of extracellular matrix (ECM) were studied. MKN45 cells were more invasive than were the MKN28 cells. Immunostaining revealed dense lamellar accumulation of fibronectin (FN) around the tumors. Along the front of the invasive MKN45 growth, however, the FN fibers were discontinuous and/or had completely vanished; the MKN28 tumor showed no FN fiber disconnection. ECM components other than FN never displayed such peritumoral massive accumulation. Cocultivation of human fibroblasts with MKN45 cells, more evidently than with MKN28 cells, revealed degradation of FN produced by fibroblasts in contact with each tumor. Both cell lines produced several FN-degrading enzymes in serum-free cultures. Proteases from the MKN45 medium were more active than were those of MKN28 in urokinase-type plasminogen activator (uPA) and metal-dependent serine proteinase-like proteases of 75 and 68 kDa in molecular weight (MW). Type I collagen-degrading 48-kDa protease was also detected from MKN45 medium but not from the MKN28 medium. MKN28 cells secreted other kinds of FN-degrading enzymes, estimated at approximate MWs of 29 and 100-150 kDa. We found no distinct differences in capacity to produce ECM components or ability to adhere to purified ECM components between these two cell lines. From these results we conclude that the stromal invasion of these cells into the subcutaneous tissue of nude mice is profoundly related to their FN-degrading capability. This capability may be catalyzed by uPA and/or metal-dependent serine proteinase-like proteases of 75 and 68 kDa.
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PMID:Fibronectin degradation by human gastric carcinoma cell lines and its associated proteases in relation to stromal invasion in nude mice. 129 40

A new human extrahepatic bile duct carcinoma cell line (KMBC) was established from a serially transplanted tumor in nude mice that originated from a surgically resected tumor from a 73-year-old Japanese man; the cell line has been maintained for 5 five years. KMBC cells proliferate in a monolayered sheet with a population doubling time of 30 hours. Chromosome number was distributed in a range from 37 to 44, with modal numbers of 40 and 41. KMBC cells and the reconstituted tumor in a nude mouse showed moderately to poorly differentiated adenocarcinoma and possessed various functional characteristics of extrahepatic bile duct carcinoma. KMBC cells secreted carbohydrate antigen 19-9, tissue polypeptide antigen, carcinoembryonic antigen, ferritin, beta 2-microglobulin, fibronectin, and alpha 2-macroglobulin and produced glutamic oxaloacetic transaminase and alkaline phosphatase. KMBC is the second established cell line that originated from a human extrahepatic bile duct carcinoma in the world literature, and it will be applicable to various experiments.
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PMID:Establishment and characterization of a new human extrahepatic bile duct carcinoma cell line (KMBC). 131 90

We have examined the role of growth factors and extracellular matrix in the proliferation and cell adhesion of a murine mammary carcinoma, SP1, and a stable highly metastatic variant, SP1-3M. On fibronectin, both cell types proliferated strongly in response to basic fibroblast growth factor (bFGF) and platelet-derived growth factor BB (PDGF-BB) after culture for 24 h and 72 h. In contrast, on collagen type I, SP1 cells proliferated only weakly to PDGF-BB at either time, and SP1-3M cells showed a response to PDGF-BB only at 72 h. The proliferative response to bFGF was also consistently lower when the cells were cultured on collagen than on fibronectin. No significant proliferative responses were detected to epithelial growth factor (EGF), transforming growth factor-beta (TGF-beta), or estrogen on any substratum. The lack of responsiveness to PDGF-BB of cells cultured on collagen type I was not due to differences in numbers or affinity of PDGF receptors. We therefore examined the adhesion and spreading properties of SP1 and SP1-3M cells. Without exogenous growth factors, both cell lines adhered to fibronectin and laminin. SP1-3M cells did not bind to collagen type I, whereas SP1 cells did. Attachment to all three substrata was inhibited by anti-beta 1 integrin IgG, suggesting that the primary adhesion to these substrata is mediated by beta 1 integrins. SP1 and SP1-3M cells showed similar integrin patterns following immunoprecipitation by anti-beta 1 integrin IgG. bFGF stimulated increased adhesion and spreading of both SP1 and SP1-3M cells to collagen type I within 24 h, whereas PDGF-BB was less capable of this effect. Our results suggest that the proliferative response of SP1 and SP1-3M cells to PDGF-BB and bFGF is dependent on the extracellular matrix environment, and imply that modification of extracellular matrix and/or surface integrin receptors may regulate responsiveness to these growth factors in the SP1 tumor model.
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PMID:Modulation of growth factor responsiveness of murine mammary carcinoma cells by cell matrix interactions: correlation of cell proliferation and spreading. 132 15

The expression of the VLA-integrins alpha 2, alpha 3, alpha 5 and alpha 6 was studied immunohistochemically in tissue samples from ductal pancreatic cancer, chronic pancreatitis, normal pancreas and in 8 cell lines of ductal human pancreatic cancer. Furthermore, adhesion assays on purified extracellular matrix (ECM)-compounds were used to define the function of alpha 2, alpha 3, alpha 5 and alpha 6 in pancreatic cancer cells. Immunohistochemically, VLA alpha 2 and VLA alpha 6 were moderately to strongly expressed on the basal surface of ductal and acinar cells in normal pancreatic tissue, while centro-acinar cells predominantly expressed VLA alpha 3 and VLA alpha 5. Pancreatic carcinoma showed intense staining for VLA alpha 2 and VLA alpha 6 with a diffuse distribution on the cell surface. The redistribution of VLA alpha 2 and VLA alpha 6 may reflect a loss of spatial arrangement of tumor cells and their ability to interact randomly with extracellular matrix structures during invasion and metastasis. Expression of VLA alpha 3 and VLA alpha 5 in pancreatic carcinoma was heterogeneous, ranging from moderate to weak, and was lost in about 50% of the cells. Two pancreatic carcinoma cell lines (PC 3, PC 44) were further investigated in adhesion assays. Monoclonal antibodies (MAbs) against alpha 2 (GI 9, 10-G-11) were able to inhibit tumor-cell adhesion to collagen IV (59%-72%) in both cell lines. A MAb against alpha 6 (GoH3) inhibited tumor-cell adhesion to laminin (52%-86%) in both cell lines. These results suggest that alpha 2 is a collagen-binding site and alpha 6 a laminin-binding site in pancreatic cancer cells. The anti-alpha 5-MAb SAM I inhibited adhesion of PC3 to fibronectin (76%), being without effect in PC44. Adhesion of both cell lines to fibronectin was almost completely inhibited by RGDS (85%-88%). Thus, alpha 5 is a functionally important fibronectin binding site in some pancreatic carcinoma cells, suggesting further RGD-dependent fibronectin binding sites in other pancreatic carcinoma cells.
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PMID:Expression and function of VLA-alpha 2, -alpha 3, -alpha 5 and -alpha 6-integrin receptors in pancreatic carcinoma. 133 Sep 37

We have screened six human squamous carcinoma cell lines for their ability to invade connective tissue by using the experimentally modified chorioallantoic membrane of a chick embryo as an in vivo model of invasion. In confirmation of our earlier studies, all the invasive cell lines expressed high levels of surface-bound urokinase type plasminogen activator (uPA). However, some cell lines expressing this activity were not invasive, suggesting that surface uPA, although necessary, was not sufficient. Since in addition to fibronectin, that can be degraded by uPA or plasmin, chorioallantoic membrane connective tissue contains collagen, we examined the profile of collagenases secreted by the various cell lines in search for an activity that would coincide with the invasive phenotype. We found, using gelatin substrate gels, that type IV gelatinase was produced by all six cell types tested, three cell types produced the M(r) 92,000 gelatinase, and three a lower-molecular-weight activity, which we identified by immunoprecipitation with specific antibodies, and by a direct assay of activity, as interstitial collagenase. Only the latter cells were found to be highly invasive. We showed previously that continuous culture in vitro of one of the carcinoma cell lines, HEp3, led to a gradual extinction of their malignant phenotype. To confirm the correlation between invasion and the production of interstitial collagenase, we examined these two functions in cells freshly isolated from a HEp3 tumor and intermittently during passage in vitro. We found that, although the surface uPA activity was slightly diminished in the in vitro grown cultures, it was still within the range of values found in highly malignant cells, suggesting that it is not the reason for the decrease in invasiveness. In contrast, the reduction in interstitial collagenase closely followed the loss of the invasive phenotype; after 30 in vitro passages the cells were almost completely devoid of interstitial collagenase and unable to invade. The decrease in collagenase activity was not the result of an increased tissue inhibitor of metalloproteinases production.
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PMID:Invasion of connective tissue by human carcinoma cell lines: requirement for urokinase, urokinase receptor, and interstitial collagenase. 133 82

Thrombospondin (TSP), which plays an important hemostatic role, is a 450-kd cytoadhesive protein present in the alpha granules of platelets. In vitro experiments using cultured malignant cells suggest that it may help to mediate malignant cell attachment to extracellular matrix and may be important in cancer invasiveness. The authors studied a group of malignant and benign breast tissues for the expression of TSP and provide evidence that TSP may have a role in tumor invasiveness. Using immunohistochemical techniques, the authors found in 48 fresh specimens of breast carcinoma that TSP stained strongly in the desmoplastic stroma or at the basement membrane associated with the malignant ductal epithelium. Tumor cells abutting these tissues revealed cytoplasmic staining for TSP. Stronger TSP staining was seen in the poorly differentiated tumors. These findings were compared with those of normal and benign breast tissue, which showed no TSP staining apart from reactivity in the large distended cysts of fibrocystic disease and faint staining in the stroma of fibroadenomas. Staining for integrin was positive in lymphocytes of both malignant and benign breast disease and equivocally also in the stromal cells of the breast cancer tissue. Immunoreactivity to TSP in tissues was also compared with that of fibronectin, laminin, and collagen type I, III, and IV. The overall findings suggest that thrombospondin may have a role in the tumor biology of invasiveness.
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PMID:Thrombospondin and other possible related matrix proteins in malignant and benign breast disease. An immunohistochemical study. 135 69


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