Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It seems certain that COX-2 is related to tumor and some data suggested that COX-2 might have relation to tumor malignance and angiogenesis. In order to elucidate the relationship between COX-2 and tumor invasive and angiogenic ability, we transfected human transitional cell carcinoma (TCC) cell line, EJ, permanently with a COX-2 expression vector or the mock vector. The EJ-COX(2) cells, which overexpressed COX-2, acquired increased invasiveness and angiogenic ability by activation of VEGF, uPA, and MMP-2. Increased invasiveness and angiogenic ability were reversed by treatment with either selective COX-2 inhibitor, NS-398, or dual COX inhibitor, indomethacin. These results demonstrate that overexpression of COX-2 can lead to phenotypic changes that alter the metastatic and angiogenic potential of TCC cancer cells.
 ...
PMID:Cyclooxygenase-2 increased the angiogenic and metastatic potential of tumor cells. 1247 Jun 62

Cells that have acquired a proliferative advantage form islets of hyperplasia during the initial stages of tumor development. Like normal cells, they require oxygen and nutrients to survive and proliferate. The centre of the islets is characterized by low oxygen pressure and low pH, conditions that stimulate the sprouting of new capillaries from nearby vascular beds. It is now well established that neovascularisation (angiogenesis) of the hyperplasias is essential for further development of the tumor. The family of ras oncogenes promotes the initiation of tumor growth by stimulating tumor cell proliferation, but also ensures tumor progression by stimulating tumor-associated angiogenesis. Oncogenic Ras proteins stimulate a number of effector pathways that culminate in the transcriptional activation of genes that control angiogenesis. Moreover, Ras signaling leads to stabilization of the produced mRNAs and, possibly, to enhanced initiation of their translation. In this review we describe the mechanisms that underlie Ras regulation of vascular endothelial growth factor (VEGF), cyclooxygenases (COX-1/-2), thrombospondins (TSP-1/-2), urokinase plasminogen activator (uPA) and matrix metalloproteases-2 and -9 (MMP-2/-9). As a result of these Ras-regulated changes in gene expression, the tumor cells cause stimulation of endothelial cells in nearby vascular beds (directly via VEGF, and indirectly via COX-produced prostaglandins) and promote remodeling of the extracellular matrix (by lowering TSP and increasing uPA/MMPs). The latter effect makes growth factors available for endothelial cell activation and migration. In addition, tumor cell-activated stromal cells also contribute to the stimulation of angiogenesis by further enhancing the production and secretion of pro-angiogenic factors into the tumor stroma.
 ...
PMID:Stimulation of angiogenesis by Ras proteins. 1498 65