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)

The expression and organization of the extracellular matrix component fibronectin has been analyzed in a collection of murine epidermal keratinocyte cell lines representative of different stages of mouse skin carcinogenesis. The fibroblastoid phenotype of spindle cells has been found to be associated with high levels of fibronectin expression and the ability to organize this molecule in an extracellular matrix. These observations, together with our previous analysis on the expression of cadherins, alpha 6 beta 4 integrin and the proteoglycan syndecan, indicate that profound alterations in cell adhesion behaviour occur in the last stages of tumor progression in this system. These alterations could favor the migratory and invasive phenotype of spindle cells.
Invasion Metastasis
PMID:Cell adhesion and tumor progression in mouse skin carcinogenesis: increased synthesis and organization of fibronectin is associated with the undifferentiated spindle phenotype. 765 10

Heparan sulfate (HS) functions as a co-factor in several signal-transduction systems that affect cellular growth, differentiation, adhesion and motility. HS, therefore, may also play a role in the malignant transformation of cells, tumor growth, cell invasiveness and the formation of tumor metastases. To explore this hypothesis, we analyzed the expression of HS and heparan sulfate proteoglycan (HSPG) in histological sections of human lung-cancer tissues and assayed for the presence of HSPGs in extracts of human lung-cancer cell lines, using a panel of native HS-, delta-HS- and HSPG (syndecan, glypican, CD44 and perlecan) core protein-specific monoclonal antibodies. Compared to normal epithelia, non-small-cell lung carcinomas, particularly poorly differentiated tumors, often expressed reduced amounts of the major cell surface-associated HSPGs (most consistently of syndecan-1). CD44 or CD44-variant proteins, in contrast, were found on all tumor cells, irrespective of their differentiation. Perlecan, a matrix-associated HSPG found in the basement membrane of normal bronchial epithelium, was consistently undetectable in invasive bronchogenic carcinomas. Staining reactions for native HS were consistently reduced in squamous-cell lung carcinomas, in the cells in contact with the stroma and in the less differentiated areas of these tumors. Reactions for delta-HS, however, were not reduced, suggesting a structural change in the HS of these tumor cells. Poorly differentiated adenocarcinomas, in contrast, yielded strong HS and delta-HS reactions. Marked differences in HSPG expression also were observed among various non-small-cell lung carcinoma cell lines. Our results suggest that poorly differentiated lung tumors have markedly altered patterns of HSPG expression, which may contribute to their invasive phenotype.
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PMID:Heparan sulfate proteoglycan expression in human lung-cancer cells. 922 15

The process of metastasis involves a series of sequential steps in which malignant cells are released from the primary tumor and metastasize to distant sites. Syndecan-1 is a cell surface proteoglycan that mediates cell adhesion and undergoes changes upon cell transformation of some cells that may contribute to the process of metastasis. To investigate the possible role of syndecan-1 in cell proliferation and metastatic potential, we employed a highly metastatic cell line (KLN 205) derived from mouse lung squamous cell carcinoma that expressed moderate amounts of syndecan-1. At first, endogenous syndecan-1 production was inhibited by an antisense oligodeoxynucleotides (ODNs). Since antisense ODNs of syndecan-1 inhibited cell growth, we established stable transfectants of syndecan-1 in this cell line to examine a proliferative advantage with the level of syndecan-1 expression. Overexpresser cells grew at a significantly faster rate than the vector-transfected control and showed greater incidence of tumor formation when injected subcutaneously into nude mice. Surprisingly, overexpresser cells enhanced pulmonary metastasis when injected intravenously. These results indicate that syndecan-1 expression plays a role in the control of cell proliferation and suggest that syndecan-1 expression may be involved in facilitating distant metastasis of tumor cells once they managed to enter the bloodstream (after intravasation steps).
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PMID:Altered proliferative and metastatic potential associated with increased expression of syndecan-1. 981 73

The prognostic value of the immunohistochemical expression of epithelial and stromal syndecan-1 was evaluated in 296 patients with gastric carcinoma. Formalin-fixed, paraffin-embedded specimens of gastric adenocarcinomas were stained with mouse monoclonal antibody B-B4 against human syndecan-1. Loss of immunoreactivity (syndecan-1 immunoreactivity correlated with a higher stage of disease (stages II-IV), tumour location in the upper third of the stomach, nodal metastases (N1 or N2), positive stromal syndecan-1 staining, deep tumour penetration (to subserosa or deeper = T2-T4), larger tumour size (> or = 5 cm) and intestinal type of cancer. No correlation between epithelial syndecan-1 immunoreactivity and age, gender, distant metastases, grade of differentiation or Borrmann classification was observed. Positive stromal syndecan-1 immunoreactivity correlated with decreased epithelial syndecan-1 expression, intestinal type of cancer and Borrmann type I. Patients with low epithelial syndecan-1 expression in cancer cells had worse overall survival than patients with strong epithelial syndecan-1 staining (p = 0.0012). Stromal syndecan-1-positive patients had a worse outcome than patients with syndecan-1-negative stroma (p = 0.0193). In Cox multivariate analysis, stromal syndecan-1 immunoreactivity was a prognostic factor independent of TNM stage, surgery for cure and tumour size. Thus, the immunohistochemical expression of syndecan-1 might be a predictor of outcome in patients with gastric adenocarcinoma.
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PMID:Epithelial and stromal syndecan-1 expression as predictor of outcome in patients with gastric cancer. 1124 2

Syndecan-1 is a multifunctional transmembrane heparan sulphate proteoglycan (HSPG) that is present on a variety of cell types. The extracellular syndecan domains can be shed from the cell surface in a highly regulated process called ectodomain shedding. We studied the influence of soluble syndecan-1 on outcome in 88 small cell lung cancer (SCLC) patients treated within the context of two randomised clinical trials with platinum-based therapy. Serum syndecan-1 concentrations were determined using enzyme-linked immunosorbent assay (ELISA) from sera taken prior to initiation of chemotherapy. Patients with the serum syndecan-1 level within the highest tertile (>212 microg/l) had only 38% 1-year and 3% 2-year survival, whereas 58% of those with a lower serum level survived for 1 year and 25% for 2 years following the diagnosis (P=0.0034). A high serum syndecan-1 level (>212 microg/l) was associated with a high pretreatment lactate dehydrogenase (LDH) level (P=0.0024) and a poor Karnofsky's performance status (P=0.021), but not with the clinical stage or the presence of distant metastases at diagnosis. A high serum syndecan-1 level had independent influence on survival also in a multivariate analysis (the relative risk, RR, 1.68; 95% CI, 1.02-2.77; P=0.044) together with the clinical stage (RR, 1.72; 95% CI, 1.05-2.82; P=0.032). We conclude that high pretreatment serum syndecan-1 level is associated with poor prognosis in SCLC treated with platinum-based chemotherapy.
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PMID:Pretreatment serum syndecan-1 levels and outcome in small cell lung cancer patients treated with platinum-based chemotherapy. 1287 80

Syndecan-1 (CD138), a cell-surface heparan sulfate proteoglycan, is involved in cell-cell, cell-matrix interaction and growth factor binding. Loss of expression of syndecan-1 in tumor cells leads to decreased intercellular cohesion, increased potential for tumor invasiveness, and metastatic spread. Furthermore, induction of syndecan-1 expression in the tumor stroma has been postulated to promote tumor angiogenesis via its binding to growth factors such as basic fibroblast growth factor. Although syndecan-1 expression within tumor cells has been investigated in head and neck squamous cell carcinoma, stromal expression has not been studied in detail. We analyzed 38 cases of head and neck squamous cell carcinoma by immunohistochemical staining for syndecan-1 expression within the stroma. The expression of syndecan-1 within tumor cells of various histologic grades of differentiation, squamous cell carcinoma in situ cells, and benign squamous epithelium was also determined. Variable levels of diminished syndecan-1 expression were noted within the dysplastic cells of 9 of 16 (60%) squamous cell carcinoma in situ lesions and in all 38 (100%) invasive squamous cell carcinoma. In general, higher levels of syndecan-1 expression were observed in the well-differentiated tumors, in contrast to significant reduction of expression seen in poorly differentiated tumors. Syndecan-1 expression was observed within the stroma (in fibroblasts) surrounding infiltrating carcinoma cells in 28 of 38 (74%) cases. The intensity of syndecan-1 staining within the stroma showed generally an inverse correlation with the degree of tumor cell differentiation. Syndecan-1 expression was not detected in the stroma beneath normal squamous epithelium or adjacent to areas of squamous cell carcinoma in situ. We conclude that induced expression of syndecan-1 in the stroma surrounding tumor cells of invasive head and neck squamous cell carcinoma is a frequent event. The increased stromal syndecan-1 expression, coupled with its loss from the surface of carcinoma cells, may contribute to tumor cell invasion and the development of metastases.
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PMID:Induced expression of syndecan-1 in the stroma of head and neck squamous cell carcinoma. 1292 Feb 24

Syndecan-1, a cell-surface transmembrane heparan sulfate proteoglycan, has been reported to correlate with the biologic behavior of malignant tumors in various organs. We examined the correlation between the expression of syndecan-1 at the protein and mRNA levels and clinicopathologic features of 37 intrahepatic cholangiocarcinomas (ICCs). Noncancerous bile duct epithelial cells showed basolateral membranous expression of syndecan-1, whereas ICC cells showed membranous and also diffuse cytoplasmic expression. In situ hybridization demonstrated a distribution of syndecan-1 mRNA similar to that of the protein in carcinoma tissue, suggesting that syndecan-1 expression in ICC is regulated at the transcriptional level. Reduction of syndecan-1 expression in carcinoma was associated with poor histological differentiation (P <0.01): syndecan-1 expression was intense and extensive in well-differentiated (10 cases) and largely negative or weakly positive in poorly differentiated (13 cases) adenocarcinoma, and its expression in moderately differentiated tumors (14 cases) was intermediate. Patients with ICCs demonstrating negative or weak expression of syndecan-1 frequently had lymph node metastases and had a rather poor prognosis after surgical resection compared with those whose tumors demonstrated moderate or strong expression (P <0.05). However, syndecan-1 expression was not correlated with tumor size, stromal desmoplasia, gross classification, vascular invasion, or perineural invasion. We conclude that expression of syndecan-1 could correlate with some aspects of the biologic behaviors of ICCs and may be a useful prognostic marker.
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PMID:Reduced expression of syndecan-1 correlates with histologic dedifferentiation, lymph node metastasis, and poor prognosis in intrahepatic cholangiocarcinoma. 1456 80

Androgen withdrawal is the only effective therapy for patients with advanced prostate cancer, but progression to androgen independence ultimately occurs in almost all patients. Novel therapeutic strategies targeting molecular mechanisms that mediate resistance to hormonal and chemotherapeutic treatment are highly warranted. Here, we aimed to evaluate the expression of potential therapeutic targets in advanced prostate cancer. A tissue microarray (TMA) containing samples from 535 tissue blocks was constructed, including benign prostatic hyperplasia as controls (n = 65), prostatic intraepithelial neoplasia (PIN; n = 78), clinically localized prostate cancers (n = 181), as well as hormone-refractory local recurrences (n = 120) and distant metastases (n = 91). The expression of 13 different proteins was analyzed using immunohistochemistry (Bcl-2, p53, ILK, Syndecan-1, MUC-1, EGFR, HER2/neu, HSP-90, Ep-CAM, MMP-2, CD-10, CD-117 and Ki67). Significant overexpression in hormone-refractory prostate cancer and metastatic tissue compared to localized prostate cancer was found for Ki67 (64% vs. 9%), Bcl-2 (11% vs. 1%), p53 (35% vs. 4%), Syndecan-1 (38% vs. 3%), EGFR (16% vs. 1%) and HER2/neu (16% vs. 0%). Overexpression of CD-117 was restricted to 1 single metastasis. All other markers did not show relevant differences in expression between subgroups. Taken together, p53, Bcl-2, Syndecan-1, EGFR and HER2/neu are preferentially expressed in hormone-refractory and metastatic prostate cancer. Selected inhibition of these targets might offer a strategy to treat advanced tumors and prevent further progression. Treatment decisions should not be based on findings in primary tumors but rather on tissues from recurrent or metastatic lesions.
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PMID:Expression patterns of potential therapeutic targets in prostate cancer. 1547 3

CD138/Syndecan-1 is a cell-surface heparan sulfate proteoglycan expressed on most epithelial cells, and decreased CD138 expression is associated with increased invasive and metastatic potential in carcinomas. CD138 expression has not been investigated previously in renal neoplasms. Formalin-fixed, paraffin-embedded tissue sections of 50 renal cell carcinomas (RCCs) (40 clear-cell RCCs of various nuclear grades, 10 of which harbored metastases; 6 papillary RCCs, 4 chromophobe RCCs) and 4 oncocytomas were stained immunohistochemically for CD138 using the monoclonal antibody B-B4 (CD138). Staining intensity and distribution were scored and results related to histologic type, nuclear grade, and local stage (pT). Immunoreactivity was membranous in all clear-cell RCCs, chromophobe RCCs, and oncocytomas and was located at the basal aspect of cytoplasm in papillary RCCs. In clear-cell RCCs, the extent of CD138 immunoreactivity decreased with increasing nuclear grade (P<0.001). No significant correlation was found between CD138 immunoreactivity and histologic type (P=0.2) or local stage (P=0.7). Metastatic foci showed a mild to moderate decrease in intensity compared with primary tumor. Decreased expression of CD138 may have a role in more aggressive behavior of clear-cell RCC.
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PMID:Expression of CD138 (Syndecan-1) in renal cell carcinoma is reduced with increasing nuclear grade. 1678 85

It has become clear that particular microRNAs (miRNAs) function either as tumour suppressors or oncogenes, whose loss or overexpression, respectively, has diagnostic and prognostic significance. In several cases, miRNAs have been shown to affect target genes that are involved in the control of cell proliferation and apoptosis. However, malignant tumours display additional traits beyond the acquisition of enhanced growth potential and decreased cell death. Malignant disease is associated with altered tumour-host interactions leading to sustained angiogenesis and the ability to invade and metastasize. It is possible that miRNAs may act as master regulators of these aspects of tumour biology. Bioinformatic analysis of putative miRNA binding sites has indicated several novel potential gene targets of cancer-associated miRNAs that function in aspects of cell adhesion, neovascularization and tissue invasion. Among others, we speculate that miRNAs may find new roles in the regulation of E-cadherin, integrin alphavbeta3, hypoxia-inducible factor-1alpha, syndecan-1, lysyl oxidase, adamalysin metalloproteinase-17, tissue inhibitors of metalloproteinase-3, c-Met and CXCR-4 that underpin the tissue architectural changes associated with malignancy.
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PMID:MicroRNAs and the hallmarks of cancer. 1702 96


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