Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyaluronan (HA) is one of the extracellular-matrix components involved in wound healing, tumour growth and metastasis. Due to the limited data on HA expression in benign and malignant breast lesions, we analyzed its presence in these lesions by using the biotinylated-hyaluronan-binding region and the link-protein complex (bHABC) of cartilage proteoglycan as a specific probe. In all benign breast lesions, the expression of HA was restricted to the stromal connective tissue, the ductal epithelial cells being completely devoid of HA. In malignant breast tumours, the intensity of stromal HA staining was significantly stronger than in benign lesions. In addition, HA was detected on cell membranes or in cytoplasms of adenocarcinoma cells, in some cases of ductal carcinoma in situ and in 31% of malignant tumours. The staining pattern was mostly similar in all breast-cancer types studied, i.e., ductal, lobular, tubular, mucinous and medullary. In ductal breast cancer, intense HA expression in stroma and carcinoma cells correlated statistically significantly to poor differentiation of carcinoma, suggesting that altered HA expression may affect the mechanisms of breast-cancer progression.
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PMID:Expression of hyaluronan in benign and malignant breast lesions. 935 68

Lumican mRNA has been identified as being differentially expressed between different regions of the same human breast tumor. In situ hybridization study of 26 independent breast tumors confirmed the presence of lumican mRNA in fibroblast-like cells within stroma and showed a significant increase of its expression in tumor compared to adjacent normal stroma (P < 0.001). Higher lumican expression was associated with higher tumor grade, lower estrogen receptor levels in the tumor, and younger age of the patients (P < 0.05). Reverse transcription-PCR analysis of total RNA extracted from 19 independent breast tissues exhibiting lesions that are thought to parallel tumor progression also suggests that this proteoglycan is differentially expressed during tumor progression.
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PMID:Expression of lumican in human breast carcinoma. 953 27

Progression to malignancy of transformed cells involves complex genetic alterations and aberrant gene expression patterns. While aberrant gene expression is often caused by alterations in individual genes, the contribution of the tumoral environment to the triggering of this gene expression is less well established. The stable but heterogeneous expression in cultured EL4/13 cells of a novel tumor-associated antigen, designated as HTgp-175, was chosen for the investigation of gene expression during tumor formation. Homogeneously HTgp-175-negative EL4/13 cells, isolated by cell sorting or obtained by subcloning, acquired HTgp-175 expression as a result of tumor formation. The tumorigenicity of HTgp-175-negative vs. HTgp-175-positive EL4 variants was identical, indicating that induction but not selection accounted for the phenotypic switch from HTgp-175-negative to HTgp-175-positive. Although mutagenesis experiments showed that the protein was not essential for tumor establishment, tumor-derived cells showed increased malignancy, linking HTgp-175 expression with genetic changes accompanying tumor progression. This novel gene expression was not an isolated event, since it was accompanied by ectopic expression of the large chondroitin sulfate proteoglycan PG-M and of normal differentiation antigens. We conclude that signals derived from the tumoral microenvironment contribute significantly to the aberrant gene expression pattern of malignant cells, apparently by fortuitous activation of differentiation processes and cause expression of novel differentiation antigens as well as of inappropriate tumor-associated and ectopic antigens.
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PMID:Differentiation of EL4 lymphoma cells by tumoral environment is associated with inappropriate expression of the large chondroitin sulfate proteoglycan PG-M and the tumor-associated antigen HTgp-175. 979 41

Decorin is a member of the small leucine-rich proteoglycan (SLRP) gene family that has recently become a focus in various areas of cancer research. The decorin protein consists of a core protein and a covalently linked glycosaminoglycan chain. Decorin binds to collagens type I, II and IV in vivo and promotes the formation of fibers with increased stability and changes in solubility. Further, the decorin core protein binds to growth factors, including transforming growth factor-beta (TGF-beta), to other intercellular matrix molecules such as fibronectin and thrombospondin, and to the decorin endocytosis receptor. Decorin may directly interfere with the cell cycle via the induction of p21WAF1/CIP1 (p21), a potent inhibitor of cyclin-dependent kinases (CDKs). Here, we discuss interactions of decorin with TGF-beta and with p21, both of which are relevant to carcinogenesis and tumor progression. TGF-beta is released by tumors of various histogenetic origins and promotes immunosuppression in the host and tumor immune escape by induction of growth arrest and apoptosis in immune cells, by downregulation of MHC II antigen expression and by changes in the cytokine release profiles of immune and tumor cells. Moreover, TGF-beta may modulate tumor growth in an autocrine and paracrine fashion, may mediate drug resistance, and may facilitate tumor angiogenesis. Decorin binds to TGF-beta, thus inhibiting its bioactivity, and is a direct or indirect negative modulator of TGF-beta synthesis. Ectopic expression of decorin results in the regression of rat C6 gliomas, an antineoplastic effect attributed to the reversal of TGF-beta-induced immunosuppression. On the other hand, de novo expression of decorin in colon cancer cells and some other tumor cells, even though not in glioma cells, results in an upregulation of p21 expression and a cell cycle arrest, presumably in a TGF-beta-independent manner. Decorin expression is downregulated in many tumors but upregulated in the peritumoral stroma. By virtue of its growth regulatory and immunomodulatory properties, decorin promises to become a novel target for the experimental therapy of human cancers.
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PMID:Transforming growth factor-beta and p-21: multiple molecular targets of decorin-mediated suppression of neoplastic growth. 1038 66

The recently developed cDNA expression array technique can be used to generate gene-expression fingerprints of tumour specimens. To gain insight into molecular mechanisms involved in the development and progression of cancer, this cDNA expression array technique could be a useful tool, however, no established methods for interpreting the results are yet available. We used the Atlas cancer cDNA expression array (Clontech, USA) for analysing total RNA isolated from four human endometrial carcinoma samples (two cell-lines and two tissue samples), one benign endometrial tissue sample and a human breast cancer cell-line, in order to develop a method for analysing the array data. The obtained gene-expression profiles were highly reproducible. XY-scatterplots and regression analysis of the logarithmic transformed data provided a practical method to analyse the data without the need of preceding normalization. Three genes (Decorin, TIMP3 and Cyclin D1) were identified to be differentially expressed between the benign endometrial tissue sample and the endometrial carcinoma samples (tissue and cell-lines). These three genes may potentially be involved in cancer progression. A higher degree of similarity in gene-expression profile was found between the endometrial samples (tissue and cell-lines) than between the endometrial samples and the breast cancer cell-line, which is indicative for an endometrial tissue-specific gene-expression profile.
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PMID:Gene expression profiles of human endometrial cancer samples using a cDNA-expression array technique: assessment of an analysis method. 1090 78

Motility factors, e.g. SF/HGF (scatter factor/hepatocyte growth factor) or AMF (autocrine motility factor) can influence the migration of tumor cells in vitro and may facilitate invasive growth and metastases in vivo. The production of motility factors was studied in cell lines derived from human cholangiocarcinomas. Culture supernatants from 5 different cholangiocarcinoma cell lines (EGI-1, RPMI 7451, MZ CHA-1, MZ CHA-2 and MZ CHA-3) were analyzed in scatter assays with NRK and MDCK cells as indicator cells which react with cellular migration in the presence of motility factors. Culture supernatants from 4 of the 5 cell lines investigated induced migration of the indicator cells thus demonstrating the production of motility factors. Three of the cell lines (MZ CHA-1, MZ CHA-2, RPMI 7451) produced a factor with a molecular weight ranging between 50 and 100 kDa, EGI-1 cells secreted a factor with a molecular weight >100 kDa. None of the factors was identical to HGF as demonstrated by the lacking reactivity in a HGF specific ELISA and by the inability to induce scattering of HPAF indicator cells like HGF. Similar to SF/HGF, the activity of the EGI-1 factor was inhibited by the proteoglycan heparin and stimulated the chemotactic cell migration, but in contrast to SF/HGF it could not induce invasive growth of NRK cells. The production of scatter factors could be involved in tumor progression and formation of metastases of cholangiocarcinomas.
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PMID:Motility factors identified in supernatants of human cholangiocarcinoma cell lines. 1129 63

Proteoglycans that modulate the activities of growth factors, chemokines, and coagulation factors regulate in turn the vascular endothelium with respect to processes such as inflammation, hemostasis, and angiogenesis. Endothelial cell-specific molecule-1 is mainly expressed by endothelial cells and regulated by pro-inflammatory cytokines (Lassalle, P., Molet, S., Janin, A., Heyden, J. V., Tavernier, J., Fiers, W., Devos, R., and Tonnel, A. B. (1996) J. Biol. Chem. 271, 20458-20464). We demonstrate that this molecule is secreted as a soluble dermatan sulfate (DS) proteoglycan. This proteoglycan represents the major form either secreted by cell lines or circulating in the human bloodstream. Because this proteoglycan is specifically secreted by endothelial cells, we propose to name it endocan. The glycosaminoglycan component of endocan consists of a single DS chain covalently attached to serine 137. Endocan dose-dependently increased the hepatocyte growth factor/scatter factor (HGF/SF)-mediated proliferation of human embryonic kidney cells, whereas the nonglycanated form of endocan did not. Moreover, DS chains purified from endocan mimicked the endocan-mediated increase of cell proliferation in the presence of HGF/SF. Overall, our results demonstrate that endocan is a novel soluble dermatan sulfate proteoglycan produced by endothelial cells. Endocan regulates HGF/SF-mediated mitogenic activity and may support the function of HGF/SF not only in embryogenesis and tissue repair after injury but also in tumor progression.
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PMID:Endocan is a novel chondroitin sulfate/dermatan sulfate proteoglycan that promotes hepatocyte growth factor/scatter factor mitogenic activity. 1159 Jan 78

Understanding the details of the molecular mechanism of tumor dissemination revealed that several proteoglycan species are involved in the process but their role can be described as Janus-faced. One level of proteoglycan alterations is at the expression of their genes coding for the core protein. Characteristically, in progressing tumors two patterns emerged: loss or neoexpression of surface proteoglycans (PG) depending on the initial expression pattern of the cell type of origin. The situation is similarly complex concerning the changes of glycosaminoglycan (GAG) of the PG during tumor progression. This is due to the fact that the majority of PGs involved is hybrid molecule meaning that their core protein can be glycanated both with chondroitin and heparan sulfate. However, such an alteration in glycanation of PG may fundamentally change the function of the molecule, especially the one operating at the cell surface. Among the extracellular PGs, decorin emerged as inhibitor of progression while perlecan as a promoter of the process. Analysis of the available data indicate that during metastatization tumor cells must express at least one cell surface HSPG species from the syndecan-glypican-CD44v3 group. Furthermore, the HS-chain of these proteoglycan(s) carry important molecular signatures (suphution or epimerization patterns). Experimental data suggest that tumor cell surface heparan sulfate (PG) may provide a target for specific anti-metastatic interventions.
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PMID:Proteoglycans and tumor progression: Janus-faced molecules with contradictory functions in cancer. 1208 48

CD44 is a receptor for the matrix glycosaminoglycan hyaluronan. Proteoglycan forms of CD44 also exhibit affinity for fibronectin and collagen as well as chemokines and growth factors. CD44 plays a role in autoimmunity, inflammation, and tumor progression. Soluble CD44 (sCD44) is found in plasma, and the levels of sCD44 correlate with immune function and some malignancies. The mechanisms by which sCD44 is generated and its function are unknown. We demonstrate here that normal bronchial epithelial cells spontaneously release sCD44. Exposure to phagocyte- and bacterium-derived proteinases markedly increased the release of sCD44 from epithelial cells. The spontaneously released sCD44 was incorporated into high molecular mass complexes derived from the matrix that also contained chondroitin sulfate, fibronectin, hyaluronan, and collagens I and IV. Enzymatic digestion with proteinases liberated sCD44 from the high molecular mass complex. Consistent with the homology of CD44 to proteoglycan core and link proteins, these data suggest that CD44 spontaneously released from normal bronchial epithelial cells can accumulate as an integral component of the matrix, where it may play a role in the organization of matrices and in anchoring growth factors and chemokines to the matrix. Increases in plasma CD44 during immune activation and tumor progression therefore may be a manifestation of the matrix remodeling that occurs in the face of the enhanced proteolytic activity associated with infection, inflammation, and tumor metastasis, leading to alterations in cell-matrix interactions.
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PMID:Proteinase-mediated release of epithelial cell-associated CD44. Extracellular CD44 complexes with components of cellular matrices. 1222 94

Proteoglycan and glycosaminoglycan content was analyzed in a model of rat mammary carcinoma to study the roles of these compounds in tumorigenesis. Hyaluronic acid and proteoglycans bearing chondroitin and/or dermatan sulfate chains were detected in solid tumors obtained after subcutaneous inoculation of Walker 256 rat carcinoma cells. About 10% of sulfated glycosaminoglycan chains corresponded to heparan sulfate. The small leucine-rich proteoglycan, decorin, was identified as one of the proteoglycans, in addition to others of higher molecular weight, by cross-reaction with an antiserum raised against pig laryngeal decorin and by N-terminal amino acid sequencing. Decorin was separated from other proteoglycans by hydrophobic chromatography and its complete structure was determined. It has a molecular weight of about 85 kDa and a dermatan chain of 45 kDa with 4-sulfated disaccharides. After degradation of the glycosaminoglycan chain, three core proteins of different molecular weight (36, 46 and 56 kDa) were identified. The presence of hyaluronic acid and decorin has been reported in a variety of tumors and tumor cells. In the Walker 256 mammary carcinoma model, hyaluronic acid may play an important role in tumor progression, since it provides a more hydrated extracellular matrix. On the other hand, decorin, which is expressed by stromal cells, represents a host defense response to tumor growth.
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PMID:Decorin is one of the proteoglycans expressed in Walker 256 rat mammary carcinoma. 1288 63


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