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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Short-term maintenance of fetal rat colonic tissue in vitro has been demonstrated using a collagen matrix organ culture system. The introduction of single (v-myc, v-rasH, v-src) oncogenes or combinations of oncogenes (v-myc/rasH, v-myc/src) into normal colon mucosal elements was established using retroviral vectors, resulting in enhanced proliferation and migration of epithelial cells from the lumen of tissue implants. Expression of a single oncogene in normal colon epithelium did not result in the establishment of cell lines. In contrast, expression of cooperating oncogenic elements resulted in cell lines in greater than 80% of experiments, revealing different morphological characteristics dependent upon the oncogene combination used. Confirmation of the expression of viral transcripts was determined using Northern blot analysis and viral oncoprotein expression using Western blot analysis (p21) and an immunoprecipitation kinase assay (src). Expression of keratin filaments was lost following passaging of cell lines but could be induced by the myc/ras transformants by growth on Rat-1 feeder layers. This induction phenomenon was not observed with myc/src lines, and although these expressed high levels of sucrase isomaltase the epithelial origin of these cells is unclear. Karyotypic analysis performed on three myc/ras-transformed cell lines revealed a normal chromosome complement associated with transformation. In this report we describe a novel in vitro transformation system for normal rat colonic epithelium mediated by the introduction of oncogene elements using different retroviral vector constructs. The potential to generate cell lines representing different stages of neoplastic progression using relevant genetic components presents significant advantages for the study of cellular and molecular interactions underlying colon neoplastic progression.
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PMID:Oncogene-mediated transformation of fetal rat colon in vitro. 137 76

Cells contracting connective tissue matrices generate tractional forces in tissues. Studies of fibroblast contraction, using collagen gels in an in vitro model, demonstrate that it involves the actin cytoskeleton, specific extracellular matrix receptors and requires stimulation by exogenous promoters. Fibroblast contraction is stimulated by factors released by platelets and potentially secreted within the contracting tissue. Endothelial cells secrete a potent promoter of fibroblast contraction which has been identified as endothelin 1. The pathway through which fibroblast contraction is stimulated appears to require activation of protein kinase C. Tumor cells can also secrete endothelin. These mechanisms may be relevant to tumor progression.
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PMID:Extracellular matrix contraction by fibroblasts: peptide promoters and second messengers. 151 96

Hyaluronic acid accumulation is characteristic of mammary tumor cells, and the amount that accumulates seems to correlate with the degree of malignancy of the producing cells. We have tested directly the relationship between hyaluronic acid accumulation and the replication rate of preneoplastic mammary cells in culture. We used nontumorigenic but immortal CL-S1 mouse mammary cells that were derived from a hyperplastic alveolar nodule. Using a collagen gel culture system, we found clear differences in the growth properties of cells before and after Passages 68 to 70. Late passage cells replicated earlier and faster than early passage cells in collagen and on plastic. The rate of cycling resembled that of tumorigenic mouse mammary cells during the first week of culture. Cells seeded at low densities cycled faster than those seeded at high densities during the second week in culture. Exogenous hyaluronic acid, at 10 to 1000 micrograms/ml, neither enhanced nor inhibited CL-S1 cell growth significantly in collagen, regardless of passage. However, by the third day in collagen, late passage cells produced 7 times more total glycosaminoglycans and 12 times more hyaluronic acid per cell than did early passage cells. Late passage cells also deposited 12 times more labeled hyaluronic acid in the matrix than did early passage cells, on a per-cell basis. After a decline in the deposition of hyaluronic acid in the extracellular matrix, growth ceased. The late passage cells did not grow in soft agar, indicating that they had not become neoplastic spontaneously during passage. However, their accelerated growth rate, coupled with the synthesis and secretion of large amounts of hyaluronic acid into the extracellular matrix, may characterize a distinct step in tumor progression in preneoplastic CL-S1 cells.
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PMID:Correlation of hyaluronic acid accumulation and the growth of preneoplastic mammary cells in collagen: a longitudinal study. 158 6

Clonal cell lines were derived from rat liver epithelial cells following their transformation with either v-raf or v-raf/v-myc. Cells transformed with v-raf alone showed reduced tumor incidence and tumor growth rates when implanted into nude mice, compared to cells also expressing the v-myc oncogene. A series of additional clones isolated from a tumor obtained following inoculation of an athymic nude mouse with the v-raf-transformed rat liver epithelial cells displayed an intermediate range of tumor aggressiveness. These findings indicate that unknown genotypic and/or phenotypic changes occur during tumor formation in vivo, which are required in addition to raf activation for complete expression of the malignant phenotype. This in vitro model of tumor progression was used to examine alterations in the expression of genes related to the growth control of liver epithelial cells, which may be involved in the malignant conversion of the preneoplastic cells. A close association was observed between the increased level of expression of the transforming growth factors alpha and beta 1, the decreased expression of extracellular matrix proteins fibronectin and collagen I, and the tumor aggressiveness (latency/growth rate), suggesting a causal role for these factors in the progression of v-raf-transformed rat liver epithelial cells to the fully malignant phenotype.
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PMID:Expression of growth-related genes during tumor progression in v-raf-transformed rat liver epithelial cells. 170 45

The ovarian surface epithelium (OSE) is known to contribute to postovulatory repair of the ovarian cortex by proliferation and migration over the site of follicular rupture, and by deposition of a basement membrane. We examined the production of other extracellular matrix components in culture by OSE cells of the rat (ROSE), using immunofluorescence microscopy, electron microscopy, and proline incorporation. We compared recently explanted cells in low passage, the immortal line ROSE 239, whose growth pattern resembles low passage cultures, and the immortal line ROSE 199, which forms ridges and papillae. The epithelial nature of all three cell types was confirmed by the presence of keratin and laminin. All three cell types secreted collagen types I and III and at least one (ROSE 199) produced highly polymerized banded fibrils, which are characteristic for stromal or interstitial extracellular matrix. Simultaneous production of collagen types I and III, keratin, and laminin by cloned subpopulations ruled out an origin of the lines in mixed epithelial/fibroblast populations. The results demonstrate that OSE has the capacity to synthesize major components of connective tissue stroma. They suggest that this epithelium, in addition to its postulated proteolytic role, may also express synthetic activity in the remodelling of the ovarian cortical stroma. A capacity of OSE cells to produce stromal components autonomously might be an important factor in the formation of ovarian surface papillae and in neoplastic progression of OSE-derived ovarian carcinomas.
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PMID:Ovarian surface epithelium: autonomous production of connective tissue-type extracellular matrix. 171 May 11

Antigen expression was studied by immunohistochemistry in 133 human melanocytic skin lesions to gain insight into the initial steps of tumor development, i.e. in particular the change from melanocytes to benign nevi. We refer to the proposed progression model of Clark and co-workers. The following types of antigens were investigated: (i) intermediate filament antigens (vimentin), (ii) melanoma-associated antigens (HMB-45, NKI/C3, MA-930, LS59), (iii) proliferation-associated antigens (S-100, Ki67, Ro/SSA, calmodulin), (iv) progression-associated antigens (HLA-DR, ICAM-1), and (v) basal membrane antigens (bullous pemphigoid antigen, laminin, fibronectin, collagen type IV). The intensity of expression and the topography of immunoreactive pigment cells were compared with the stage of tumor progression. Special attention was paid to the early steps of this process, i.e. the disturbance of the epidermal melanin unit and the development of melanocytic ("nevocellular")nevi. A dramatic shift of antigen expression (antigen types [i] to [v]) was noted in benign nevi compared with melanocytes. Nevi with cellular atypia disclosed a tendency towards an increased percentage of tumor cells reactive for melanoma- and progression-related antigens (types [ii] and [iv]). However, there was no clear cut level of distinction of antigen expression (types [i] to [v]) between benign and primary malignant melanocytic tumors. So-called dysplastic nevi resembled benign tumors or melanocytes rather than malignant melanoma. Metastatic melanoma of skin showed a relatively high number of Ki67-positive, cycling melanoma cells. The results have a bearing on the concepts of melanocytic nevus ontogenesis and "maturation". It appears that melanocytes lose maturity on their way down to the dermis in contrast to traditional concepts (Abtropfung); this might be of importance for our understanding of melanoma development in association with melanocytic nevi. Our findings are discussed with regard to Clark's model of tumor progression.
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PMID:The initial steps of tumor progression in melanocytic lineage: a histochemical approach. 174 97

The distribution of basement membrane type VII collagen was detected immunohistochemically and compared in normal human organs and their neoplastic derivatives using monoclonal antibody LH7.2. In normal tissues, type VII collagen was found to be restricted to the basement membrane surrounding or underlying combined epithelia, such as those lining breast, prostate, and bronchus, which are composed of a basal and luminal cell layer, and stratified epithelia, such as larynx, esophagus, trachea, vagina, ectocervix, and epidermis. No type VII collagen was found in the "simple' epithelia lining the major part of the gastrointestinal tract (GI) tract, such as liver, stomach, and intestine, or around blood vessels, muscle, and nerve fibers, which are surrounded, however, by a basement membrane containing type IV collagen and laminin. When tested in benign and malignant local tumors, antibody LH7.2 showed staining patterns partly similar to those observed in the corresponding normal tissues. This resulted in a well-circumscribed positive reaction around ducts in carcinomas in situ of the breast, in benign prostate tumors, in pleomorphic adenomas, and in a negative reaction in tumors of the GI tract. Furthermore type VII collagen was predominantly seen in carcinomas with a squamous differentiation, such as squamous carcinomas of the lung, head and neck, vulva, and vagina. These results indicate that the presence of type VII collagen in malignant tumors is correlated with (squamous) differentiation rather than with the origin of the tumor. With tumor progression, an increased presence of type VII collagen, as compared with normal urinary bladder, was found in infiltrating transitional cell carcinomas. Thus, although in general invasive and metastatic tumors do not express extensively type VII collagen, exceptions to this rule exist in bladder cancer, squamous carcinomas of the lung, tumors of the head and neck region, female genital tract tumors, and in some adenocarcinomas of the breast.
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PMID:Distribution patterns of type VII collagen in normal and malignant human tissues. 186 28

The expression of the integrin receptors VLA-1, -2, -3, and -6 was studied in normal cultured melanocytes and in five melanoma cell lines. Normal melanocytes synthesized VLA-3, but did not reveal detectable levels of VLA-1, -2, and -6. All melanoma cell lines, however, expressed VLA-2, -3, and -6. VLA-1 was synthesized by two of five melanoma lines. In parallel, we had analyzed the expression of four previously characterized melanoma cell surface antigens. One of them (antigen A.1.43), which is associated with tumor progression of human melanoma, revealed a striking similarity to VLA-2. In sequential immunoprecipitation experiments, we show that A.1.43 is identical with the integrin VLA-2, a cell surface receptor for collagen, laminin, and fibronectin.
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PMID:Identification of a melanoma progression antigen as integrin VLA-2. 199 90

The cysteine proteinase cathepsin B has been implicated in the progression of tumors from a premalignant to a malignant state. Activity of cathepsin B has been shown to be elevated in parallel with malignancy or metastatic potential of human and rodent tumors. These increases in cathepsin B activity correspond in part to increases in mRNA for cathepsin B and in part to reduced regulation by endogenous low Mr cysteine proteinase inhibitors. Most properties of tumor cathepsin B appear to be similar to those of cathepsin B from normal tissues. However, the subcellular distribution of cathepsin B is altered in tumors, resulting in association of cathepsin B with plasma membrane fractions or in release of high Mr forms of cathepsin B into the extracellular milieu. Since cathepsin B can degrade laminin, fibronectin and type IV collagen, we speculate that the presence of cathepsin B at the surface of tumor cells may contribute to the local dissolution of basement membrane observed during tumor cell extravasation. Direct evidence that cathepsin B plays a role in cancer progression awaits studies in which upregulation or downregulation of the expression of cathepsin B and its endogenous inhibitors is found to alter tumorigenesis, metastatic potential, etc.
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PMID:Cathepsin B and cystatins: evidence for a role in cancer progression. 210 90

The generation of invasiveness in transformed cells represents an essential step of tumor progression. We have previously shown that MDCK epithelial cells, which are deprived of intracellular adhesion by the addition of anti-Arc-1/uvomorulin antibodies, become invasive for collagen gels and embryonal heart tissue (Behrens, J., M. M. Mareel, F. M. Van Roy, and W. Birchmeier. 1989. J. Cell Biol. 108: 2435-2447.). Here we examined whether invasiveness is also induced by scatter factor, which is known to dissociate epithelial cells (Stoker, M., E. Gherardi, M. Perryman, and J. Gray. 1987. Nature (Lond.). 327:239-242.). Scatter factor was purified to homogeneity from conditioned medium of human fibroblasts by heparin-Sepharose chromatography, followed by cation exchange chromatography, gel filtration, or preparative SDS gel electrophoresis. We found that scatter factor represents a 92,000 mol wt glycoprotein which, apparently, is converted by limited proteolysis into disulfide-linked 62,000 and 34/32,000 mol wt subunits. Reversed phase HPLC and sequence analysis of tryptic peptides confirmed the suggested molecular structure, and revealed further that scatter factor exhibits sequence similarities to hepatocyte growth factor and to plasminogen. Purified scatter factor in fact induces the invasiveness into collagen matrices of MDCK epithelial cells, and induces or promotes the invasiveness of a number of human carcinoma cell lines. Apparently, the effect on the human cells depends on their respective degree of differentiation, i.e., cell lines with a less pronounced epithelial phenotype were more susceptible to the factor. Scatter factor does not seem to influence synthesis, steady-state level, and phosphorylation of the cell adhesion molecule Arc-1/uvomorulin. Thus, scatter factor represents a clearly defined molecular species which induces, in vitro, the progression of epithelial cells to a more motile, i.e., invasive phenotype.
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PMID:Scatter factor: molecular characteristics and effect on the invasiveness of epithelial cells. 214 76


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