Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P39060 (endostatin)
 2,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor progression is dependent in large part on angiogenesis and angiogenesis inhibitors have repeatedly been shown to inhibit tumor growth. The present study sought to determine whether the oral squamous carcinoma cells expressed and produced collagen XVIII, a known precursor of endostatin. Four established cell lines of oral squamous cell carcinoma (SCC) were employed for these studies. Quantitative Real-Time RT-PCR was used to assess the expression of collagen XVIII and CBP2/Hsp47, an ostensible chaperone for fibrillar and basement membrane collagens. Real-Time PCR assessment of collagen XVIII with primers selected to the common region of collagen XVIII revealed variable expression among cell lines of oral SCC. Conversely, the long form of collagen XVIII revealed no products. Comparatively, the lowest level of expression of CBP2/Hsp47 was observed in SCC4 that also had the lowest level of collagen XVIII. However, there was no direct relationship between the levels of CBP2/Hsp47 and collagen XVIII expression across the four cell lines. Treatment of SCC cells with CBP2/Hsp47 antisense phosphorothioate oligonucleotides modulated the production of collagen XVIII but not its expression. These findings imply that CBP2/Hsp47 may play a role in tumor progression by mediating the endogenous processing of collagen XVIII in tumor cells.
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PMID:The production of the endostatin precursor collagen XVIII in head and neck carcinomas is modulated by CBP2/Hsp47. 1217 73

The aim of this study was to evaluate the histopathologic features and the expression of angiogenesis-related markers in primary tumors and metastatic lymph nodes of oral squamous cell carcinomas (SCCs) with multiple lymph node involvement in comparison with oral SCCs without nodal metastasis. The protein levels of the angiogenesis inhibitor endostatin, as well as those of the related molecules collagen XVIII, collagen-binding protein (CBP) 2/heat shock protein (HSP) 47, and cathepsin L, were evaluated by immunohistochemical analysis. Compared with nonmetastatic cases, primary tumors of the metastatic group exhibited significantly decreased protein levels of endostatin and its precursor collagen XVIII. Comparison between primary tumors and positive nodes of the metastatic cases revealed decreased expression of collagen XVIII and CBP2/HSP47 in metastases. Angiogenesis is essential for tumor growth and metastasis; accordingly, the observed differences in the immunohistochemical expression of angiogenesis-related proteins in oral SCC with multiple lymph node involvement may provide an explanation for the increased metastatic potential of these tumors.
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PMID:Immunohistochemical expression of angiogenesis-related markers in oral squamous cell carcinomas with multiple metastatic lymph nodes. 1271 Jan 30

The present study sought to determine the potential role of stress activated MAPK and phosphatidylinositol 3-kinase (PI3K) signaling pathways in mediating phenotypic switching between angiogenic and angiostatic elements among squamous cell carcinoma (SCC) cell lines. In particular, we investigated the effects of hypoxia and those of cobalt chloride (CoCl(2)), which mimics the hypoxic response including the production of reactive oxygen species, on such phenotypic shifts. The expression and production of collagen XVIII, and CBP2/Hsp47 provided a measure of an angiostatic phenotype, while vascular endothelial growth factor (VEGF) expression was used to assess potential angiogenic states. These studies revealed that hypoxia produced a slight up-regulation of collagen XVIII and CBP2/Hsp47 that was inhibited by the stress kinase inhibitor SB203580 but was unaffected by N-acetylcysteine (NAC). In addition, VEGF expression was increased following hypoxia and this effect was reversed with inhibition of by SB203580. Conversely, CoCl(2) significantly diminished the expression of both collagen XVIII and CBP2/Hsp47 and enhanced VEGF expression. These changes were reversed by the PI3K inhibitor wortmannin and by treating cells with NAC. These studies show that phenotypic switching between collagen XVIII and VEGF is controlled by stress activated kinases under hypoxia, and PI3K signaling pathways as well as reactive oxygen species (ROS) following CoCl(2) treatment. Furthermore, modulation of the angiogenic switch is most profound during Akt activation than during activation of stress activated kinases.
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PMID:Phenotypic switching of VEGF and collagen XVIII during hypoxia in head and neck squamous carcinoma cells. 1367 10