Platelet releasate promotes breast cancer growth and angiogenesis via VEGF-integrin cooperative signalling.
Platelet releasate promotes breast cancer growth and angiogenesis via VEGF-integrin cooperative signalling.
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血小板释放物通过 VEGF-整合素协同信号促进乳腺癌生长和血管生成
DOI：
10.1038/bjc.2017.214
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发表时间：
2017-08-22
影响因子：
8.8
通讯作者：
Li N
中科院分区：
文献类型：
--
作者：
Jiang L;Luan Y;Miao X;Sun C;Li K;Huang Z;Xu D;Zhang M;Kong F;Li N
背景：促血管生成因子或抗血管生成因子选择性释放血小板可明显调节血管生成。方法：分别用富含促血管生成因子的蛋白酶激活受体1(PAR1-PR)和富含抗血管生成因子的PAR4-PR(PAR1-PR)刺激乳腺癌细胞MCF-7和MDA-MB-231，研究PAR1-PR和PAR4-PR对乳腺癌细胞增殖的影响。结果：PAR1-PR和PAR4-PR(10%)对MCF-7和MDA-MB-231细胞的增殖有相似的促进作用。癌细胞触发了血管内皮细胞的毛细血管样管的形成，而富含血管生成因子的PAR1-PR进一步促进了这一过程。血管内皮生长因子，而不是SDF-1α，受体阻断可阻断PAR1-PR/PAR4-PR促进的癌细胞增殖。RGDS阻断整合素的作用与抑制血管内皮生长因子的作用相同。Src和ERK的抑制作用减弱，而PI3K和PKC的阻断则取消了血小板释放促进的癌细胞增殖。在裸鼠皮下移植MDA-MB-231细胞模型中，PAR1-PR对肿瘤生长的促进作用比PAR4-PR更明显，并且似乎是通过促进更深层次的肿瘤血管生成来实现的。结论：血小板释放通过血管内皮生长因子-整合素协同信号通路促进乳腺癌细胞的增殖。富含促血管生成因子的血小板释放物更显著地增强了癌细胞诱导的血管生成，从而夸大了体内肿瘤的生长。
Background:Selective platelet release of pro-or anti-angiogenic factors distinctly regulated angiogenesis. We hypothesised that selective release of platelet angiogenic factors could differently regulate tumour growth.Methods:Breast cancer cell proliferation, cancer cell-induced endothelial tube formation in vitro, and tumour growth in vivo were studied in the presence of protease-activated receptor 1-stimulated platelet releasate (PAR1-PR; rich in pro-angiogenic factors) or PAR4-PR (rich in anti-angiogenic factors).Results:The PAR1-PR and PAR4-PR supplementation (10%) similarly enhanced cell proliferation of MCF-7 and MDA-MB-231 breast cancer cells. The cancer cells triggered capillary-like tube formation of endothelial cells that was further enhanced by pro-angiogenic factor-rich PAR1-PR. The VEGF, but not SDF-1α, receptor blockade abolished PAR1-PR/PAR4-PR-enhanced cancer cell proliferation. Integrin blockade by RGDS had identical effects as VEGF inhibition. The Src and ERK inhibition diminished, whereas PI3K and PKC blockade abolished platelet releasate-enhanced cancer cell proliferation. Using a model of subcutaneous implantation of MDA-MB-231 cells in nude mice, PAR1-PR enhanced tumour growth more markedly than PAR4-PR, and seemed to achieve the exaggeration by promoting more profound tumour angiogenesis.Conclusions:Platelet releasate increases breast cancer cell proliferation through VEGF–integrin cooperative signalling. Pro-angiogenic factor-rich platelet releasate enhances cancer cell-induced angiogenesis more markedly, and thus exaggerates tumour growth in vivo.
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影响因子：
28.2
作者：
Kuznetsov HS;Marsh T;Markens BA;Castaño Z;Greene-Colozzi A;Hay SA;Brown VE;Richardson AL;Signoretti S;Battinelli EM;McAllister SS
通讯作者：
McAllister SS
影响因子：
4.8
作者：
Vlahakis, Nicholas E.;Young, Bradford A.;Sheppard, Dean
通讯作者：
Sheppard, Dean
DOI：
10.1158/1078-0432.ccr-14-0870
发表时间：
2015-02-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Bottsford-Miller J;Choi HJ;Dalton HJ;Stone RL;Cho MS;Haemmerle M;Nick AM;Pradeep S;Zand B;Previs RA;Pecot CV;Crane EK;Hu W;Lutgendorf SK;Afshar-Kharghan V;Sood AK
通讯作者：
Sood AK
DOI：
10.1038/nrc3004
发表时间：
2011-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Gay LJ;Felding-Habermann B
通讯作者：
Felding-Habermann B
影响因子：
50.3
作者：
Labelle M;Begum S;Hynes RO
通讯作者：
Hynes RO