Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Versican, a proteoglycan previously reported to increase in other malignant tumours, was studied immunohistochemically in 299 primary epithelial ovarian cancers, their 43 metastases and 6 normal ovaries to evaluate its prognostic value and relation to hyaluronan, another extracellular matrix molecule increased in cancer and a binding partner of versican. The stainings were scored according to the area percentage of strong versican signal of total peri- and intratumoural stroma as low (<15%) or high (>or=15%). Epithelial staining of the tumours was scored as positive or negative. Low and high area percentage of strong stromal versican staining were observed in 133 and 166 carcinomas, respectively. A low area percentage of strong stromal versican staining correlated with mucinous histology (p = 0.019) and early International Federation of Gynecologists and Obstetritians (FIGO) stage (p < 0.0005), whereas a high percentage was associated with reduced 5-year survival rate of the patients (44% vs. 32%; p = 0.032). Versican was associated with the cancer cells in 151 tumours and correlated with clear cell histology (p < 0.0005), early FIGO stage (p = 0.049) and increased recurrence-free survival (63% vs. 47%; p = 0.032). However, in Cox's multivariate analyses with the conventional prognostic factors included, neither stromal nor cancer cell-associated versican reached a significant prognostic value. Versican is thus enriched in the malignant stroma surrounding and promoting the growth of ovarian cancer, probably acting with hyaluronan, and associates with unfavourable prognosis but does not constitute an independent indicator of patient survival.
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PMID:Versican in epithelial ovarian cancer: relation to hyaluronan, clinicopathologic factors and prognosis. 1450 34

Changes in the production and structure of glycosaminoglycans and proteoglycans have been reported in many neoplastic tissues, and versican and hyaluronan (extracellular matrix components) are frequently increased in tumours and promote tumour progression. The distribution of chondroitin sulphate, versican and hyaluronan in normal canine colonic wall (n=10), and normal colonic lymph nodes (n=10), colonic adenomas (n=22), colonic adenocarcinomas (n=28), colonic undifferentiated carcinomas (n=7), and colonic lymph node metastases (n=8), was examined, with antibodies against chondroitin sulphate and versican, and a specific biotinylated probe for hyaluronan. The epithelial cells of the normal colonic mucosa were negative for all three substances, whereas the stromal tissue and lamina propria were moderately positive for chondroitin sulphate and hyaluronan, and weakly positive for versican. Chondroitin sulphate expression was increased in adenomas and carcinomas. However, there was no significant correlation between grade of tumour and degree of chondroitin sulphate expression. Versican expression was increased in the peritumoral stroma of adenocarcinomas and reduced in adenomas. A significant correlation was observed between grade of tumour and degree of versican expression. In 13 adenocarcinomas and undifferentiated carcinomas with invasion into all layers of the colorectum, the intensity of stromal versican expression was significantly related to the depth of invasion; the intensity was increased in the stroma of tumour islands in deep layers of the colonic wall. Unlike versican expression, hyaluronan expression was increased in the stromal tissue of both adenomas and carcinomas. However, the degree of stromal hyaluronan expression was unrelated to tumour grade and depth of tumour invasion. Hyaluronan was also expressed in the membrane and in the cytoplasm of tumour cells in 3/22 (14%) adenomas, 18/28 (64%) adenocarcinomas and 2/7 (29%) undifferentiated carcinomas. These results suggest that altered levels of both versican and hyaluronan in canine colonic tumours affect tumour progression.
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PMID:Versican and hyaluronan expression in canine colonic adenomas and carcinomas: relation to malignancy and depth of tumour invasion. 1551 34

The aim of the study was to investigate the expression and prognostic role of versican in 212 patients with resected nonsmall cell lung cancer. Tumor samples were stained immunohistochemically, and the versican staining was evaluated both in tumor stroma and cancer cells. The staining results were compared to the clinical data of the patients, the tumor cell proliferation, and the expression of hyaluronan. In the whole material, low and high area percentages of stromal versican staining were observed in 135 and 77 carcinomas, respectively. Tumor cell-associated staining signal for versican was observed in 33 cases. In the whole material, the significant relationship between high stromal staining of versican and that of hyaluronan was noticed (P = .001). The expression of stromal versican was related to tumor type (P = .008) and high stromal staining was inversely correlated with poor tumor differentiation (P = .045), but not with tumor cell proliferation. Among adenocarcinomas, the high stromal staining of versican was associated with tumor recurrence (P = .024), higher tumor stage (P = .022), and lymph node metastases (P = .042). Versican expression was not related to patient outcome in the whole material, but among adenocarcinomas, the high stromal staining was related to poor disease-free survival (P = .0056). However, in Cox multivariate analysis with tumor stage, versican expression did not retain its prognostic significance. The results indicate that increased stromal versican is related to higher tumor recurrence rate and more advanced disease. Despite the important role of versican in nonsmall cell lung cancer, traditional clinicopathologic factors remained most significant in the current study.
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PMID:Versican in nonsmall cell lung cancer: relation to hyaluronan, clinicopathologic factors, and prognosis. 1571 81

The histological detection of laminin-rich vasculogenic mimicry patterns in human primary uveal melanomas is associated with death from metastases. We therefore hypothesized that highly invasive uveal melanoma cells forming vasculogenic mimicry patterns after exposure to a laminin-rich three-dimensional microenvironment would differentially express genes associated with invasive and metastatic behavior. However, we discovered that genes associated with differentiation (GDF15 and ATF3) and suppression of proliferation (CDKNa1/p21) were up-regulated in highly invasive uveal melanoma cells forming vasculogenic mimicry patterns, and genes associated with promotion of invasive and metastatic behavior such as CD44, CCNE2 (cyclin E2), THBS1 (thrombospondin 1), and CSPG2 (chondroitin sulfate proteoglycan; versican) were down-regulated. After forming vasculogenic mimicry patterns, uveal melanoma cells invaded only short distances, failed to replicate, and changed morphologically from the invasive epithelioid to the indolent spindle A phenotype. In human tissue samples, uveal melanoma cells within vasculogenic mimicry patterns assumed the spindle A morphology, and the expression of Ki67 was significantly reduced in adjacent melanoma cells. Thus, the generation of vasculogenic mimicry patterns is accompanied by dampening of the invasive and metastatic uveal melanoma genotype and phenotype and underscores the plasticity of these cells in response to cues from the microenvironment.
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PMID:Tumor cell plasticity in uveal melanoma: microenvironment directed dampening of the invasive and metastatic genotype and phenotype accompanies the generation of vasculogenic mimicry patterns. 1700 93

Tumour cells have to undergo gene expression changes in order to metastasise and adapt to a new site. We investigated these changes in liver metastases of colorectal cancer by using genome-wide microarray analysis to profile the expression of 48 primary tumours and 28 liver metastases. Statistical analysis of these expression profiles using the significance analysis of microarrays (SAM) method identified 778 genes differentially expressed between primary tumours and metastases. Gene ontology analysis revealed that genes associated with tissue remodelling and immune response were upregulated in metastases relative to primary tumours, whereas genes associated with proliferation and oxidative phosphorylation were downregulated. Quantitative real-time PCR confirmed the differential expression of selected genes, osteopontin, versican, ADAM17, CKS2, PRDX1, CXCR4, CXCL12, and LCN2. The upregulation of genes associated with tissue remodelling and immune response are likely to be involved in metastatic invasion and colonisation of the new site because these genes can promote tumour progression. However, downregulation of genes associated with proliferation suggests that proliferation in metastases was reduced relative to primary tumours.
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PMID:Genome wide expression profiling identifies genes associated with colorectal liver metastasis. 1748 16

Increased expression of the proteoglycan, versican is strongly associated with poor outcome for many different cancers. Depending on the cancer type, versican is expressed by either the cancer cells themselves or by stromal cells surrounding the tumor. Versican plays diverse roles in cell adhesion, proliferation, migration and angiogenesis, all features of invasion and metastasis. These wide ranging functions have been attributed to the central glycosaminoglycan-binding region of versican, and to the N-(G1) and C-(G3) terminal globular domains which collectively interact with a large number of extracellular matrix and cell surface structural components. Here we review the recently identified mechanisms responsible for the regulation of versican expression and the biological roles that versican plays in cancer invasion and metastasis. The regulation of versican expression may represent one mechanism whereby cancer cells alter their surrounding microenvironment to facilitate the malignant growth and invasion of several tumor types. A greater understanding of the regulation of versican expression may contribute to the development of therapeutic methods to inhibit versican function and tumor invasion.
Cancer Metastasis Rev 2009 Jun
PMID:The biological role and regulation of versican levels in cancer. 1916 15

Hyaluronan is an extracellular matrix component implicated in expansion of the extracellular space, organization of supramolecular architecture, cell motility, proliferation, tumour metastases and wound healing. Hyaluronan is highly expressed in the developing heart but it is only a minor component of the mature heart. The loss of hyaluronan synthase-2 (Has2) results in embryonic lethality with a phenotype remarkably similar to that of the versican-deficient heart defect mouse. Has2-deficient embryos lack hyaluronan-containing cardiac jelly, and at embryonic day 9.5 show arrested development, with an apparent absence of the right ventricle and underdevelopment of the conustruncus segment, and pericardial effusion consistent with heart failure. Cardiac cushions are totally absent, and endocardial cell migration over collagen gels is not detectable in Has2-deficient atrioventricular (AV) canal explants. Endothelial to mesenchymal transformation is also defective in AV explants from Has2-null embryos. The normal phenotype is restored in AV canal explants from Has2-deficient embryos by co-culture with wild type AV canal explants, with conditioned media from wild type AV explants or with exogenous hyaluronan. These results provide evidence for a direct role for hyaluronan during endocardial cushion and AV canal morphogenesis.
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PMID:Regulation of cardiac cushion development by hyaluronan. 2042 37

The assembly of pericellular matrix containing hyaluronan (HA) and versican has been shown to be a pre-requisite for proliferation and migration of mesenchymal cells. In this study, we investigated whether treatment with recombinant versican could induce the formation of a pericellular matrix by ovarian cancer cells (OVCAR-3, OVCAR-5, and SKOV-3) and promote their motility, invasion, and adhesion to peritoneal cells in vitro. We also determined whether versican-induced pericellular matrix formation and metastatic cancer cell behavior could be blocked by small HA oligosaccharides. Only combined treatment with recombinant versican and HA resulted in pericellular matrix formation by OVCAR-5 and SKOV-3 but not by OVCAR-3 cells, which lack the HA receptor, CD44. The motility of OVCAR-5 and SKOV-3 cells was significantly increased in scratch wound and chemotaxis assays following treatment with recombinant versican and HA. Versican and HA also promoted invasion of SKOV-3 and OVCAR-5 cells but had no effect on OVCAR-3 cells. We have demonstrated that exogenous HA significantly increased OVCAR-5 and SKOV-3 adhesion to peritoneal cells but adhesion was not further increased by versican treatment. Small HA oligomers (6-10 disaccharides) were able to significantly block formation of pericellular matrix by OVCAR-5 cells, as well as the increased motility and invasion induced by recombinant versican. HA oligomers also significantly blocked OVCAR-5 adhesion to peritoneal cells both in the presence and absence of exogenous HA. The dependence of CD44 for the versican and HA mediated effects were demonstrated by the inhibition of pericellular matrix formation as well as motility and invasion of OVCAR-5 cells following treatment with CD44 neutralizing antibody in the presence of versican and HA. We conclude that the acquisition of a HA/versican pericellular matrix by ovarian cancer cells increases their metastatic potential. HA oligomers can block this mechanism and are promising inhibitors of ovarian cancer dissemination.
Clin Exp Metastasis 2011 Feb
PMID:Versican induces a pro-metastatic ovarian cancer cell behavior which can be inhibited by small hyaluronan oligosaccharides. 2115 87

The extent of tumor removal determines the effectiveness of postoperative oncotherapy. This is especially true for primary brain tumors, where peritumoral invasion usually makes radical resection impossible. The aim of the study was to determinate the specific expression pattern of invasion related molecules of different intracranial tumors and to identify molecules that are principally responsible for the peritumoral invasiveness of grade II astrocytoma mRNA expression of 26 extracellular matrix (ECM) molecules was determined in tissue samples from grade II astrocytoma, schwannoma, intracerebral metastases of non-small cell lung cancer and normal brain. Immunohistochemical staining for brevican, neurocan, tenascin-C and versican was also performed for each tumor group. Comparing astrocytoma to metastasis, schwannoma and normal brain; and metastasis and schwannoma to normal brain, 22, 17, 20, 21, and 19 molecules, respectively, were found to be significantly overexpressed at the mRNA level. Cluster analysis of mRNA expression showed a specific gene expression pattern for each histological group. Four molecules of 26 were found to be associated to astrocytoma. Immunohistochemical staining confirmed the results of the mRNA analysis at the protein level. Tumors of different origin have a specific invasive phenotype that can evidently determinate on gene expression level. This characteristic expression pattern of the invasion-related molecules might help to screen exact targets for anti-invasion drugs. In case of low-grade astrocytoma. brevican, neurocan, tenascin-C and versican were found to correlate principally with the invasive phenotype of low-grade astrocytoma, thus these molecules can potentially serve as targets for anti-invasion therapy in the future.
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PMID:Brevican, neurocan, tenascin-C and versican are mainly responsible for the invasiveness of low-grade astrocytoma. 2199 79

Tumors systemically initiate metastatic niches in distant target metastatic organs. These niches, composed of bone marrow-derived hematopoietic cells, provide permissive conditions for future metastases. However, the mechanisms by which these cells mediate outgrowth of metastatic tumor cells are not completely known. Using mouse models of spontaneous breast cancer, we show enhanced recruitment of bone marrow-derived CD11b(+)Gr1(+) myeloid progenitor cells in the premetastatic lungs. Gene expression profiling revealed that the myeloid cells from metastatic lungs express versican, an extracellular matrix proteoglycan. Notably, versican in metastatic lungs was mainly contributed by the CD11b(+)Ly6C(high) monocytic fraction of the myeloid cells and not the tumor cells or other stromal cells. Versican knockdown in the bone marrow significantly impaired lung metastases in vivo, without impacting their recruitment to the lungs or altering the immune microenvironment. Versican stimulated mesenchymal to epithelial transition of metastatic tumor cells by attenuating phospho-Smad2 levels, which resulted in elevated cell proliferation and accelerated metastases. Analysis of clinical specimens showed elevated versican expression within the metastatic lung of patients with breast cancer. Together, our findings suggest that selectively targeting tumor-elicited myeloid cells or versican represents a potential therapeutic strategy for combating metastatic disease.
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PMID:Myeloid progenitor cells in the premetastatic lung promote metastases by inducing mesenchymal to epithelial transition. 2228 53


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