A role for nucleotides in support of breast cancer angiogenesis: heterologous receptor signalling.
A role for nucleotides in support of breast cancer angiogenesis: heterologous receptor signalling.
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DOI：
10.1038/bjc.2011.134
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发表时间：
2011-05-10
影响因子：
8.8
通讯作者：
Buxton, I. L. O.
中科院分区：
文献类型：
--
作者：
Yokdang, N.;Tellez, J. D.;Tian, H.;Norvell, J.;Barsky, S. H.;Valencik, M.;Buxton, I. L. O.
Human breast carcinoma cells secrete an adenosine 5′-diphosphate transphosphorylase (sNDPK) known to induce endothelial cell tubulogenesis in a P2Y receptor-dependent manner. We examined sNDPK secretion and its effects on human endothelial cells. Nucleoside diphosphate kinase (NDPK) secretion was measured by western blot and enzyme-linked immunosorbent assay, while transphosphorylase activity was measured using the luciferin-luciferase ATP assay. Activation of MAPK was determined by western blot analysis, immunofluorescence and endothelial cell proliferation and migration. A panel of breast cancer cell lines with origin as ductal carcinoma, adenocarcinoma or medullary carcinoma, secrete sNDPK-A/B. Addition of purified NDPK-B to endothelial cultures activated VEGFR-2 and Erk1/2, both of which were blocked by inhibitors of NDPK and P2Y receptors. Activation of VEGFR-2 and ErK1/2 by 2-methylthio-ATP (2MeS-ATP) was blocked by pretreatment with the P2Y1-specific antagonist MRS2179, the proto-oncogene non-receptor tyrosine kinase (Src) inhibitor PP2 or the VEGFR-2 antagonist SU1498. Nucleoside diphosphate kinase-B stimulates cell growth and migration in a concentration-dependent manner comparable to the effect of vascular endothelial growth factor. Treatment of endothelial cells with either NDPK-B or 2MeS-ATP induced migration, blocked by P2Y1, Src or VEGFR-2 antagonists. sNDPK supports angiogenesis. Understanding the mechanism of action of sNDPK and P2Y1 nucleotide signalling in metastasis and angiogenesis represent new therapeutic targets for anti-angiogenic therapies to benefit patients.
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