Vaccine and Gene Therapy Institute, Oregon Health and Science University, Portland, Oregon, USA.
PLoS One. 2013 Jul 23;8(7):e69828. doi: 10.1371/journal.pone.0069828. Print 2013.
Angiogenesis is a critical factor in the growth and dissemination of solid tumors. Indeed, tumor vasculature is abnormal and contributes to the development and spread of malignancies by creating a hostile microenvironment. The alternative SDF-1/CXCL12 receptor, CXCR7, is frequently and specifically expressed in tumor-associated vessels. In this study, we examine the role of endothelium-expressed CXCR7 in tumor vascular dysfunction by specifically examining the contribution of CXCR7 to endothelial cell (EC) proliferation. We demonstrate that CXCR7 expression is sufficient to drive post-confluent growth in EC cultures. Further, we provide a novel mechanism for CXCR7-mediated proliferation via proteasomal degradation of the tumor suppressor protein Rb. These findings identify a heretofore unappreciated role for CXCR7 in vascular dysfunction and confirm this receptor as a plausible target for anti-tumor therapy.
血管生成是实体瘤生长和扩散的关键因素。事实上，肿瘤血管是异常的，并通过创造一个恶劣的微环境促进恶性肿瘤的发展和扩散。替代的 SDF-1/CXCL12 受体 CXCR7 在肿瘤相关血管中经常且特异性表达。在这项研究中，我们通过专门研究 CXCR7 对内皮细胞 (EC) 增殖的贡献，来检验内皮细胞表达的 CXCR7 在肿瘤血管功能障碍中的作用。我们证明 CXCR7 的表达足以驱动 EC 培养物的接触后生长。此外，我们通过蛋白酶体降解肿瘤抑制蛋白 Rb 提供了一个 CXCR7 介导增殖的新机制。这些发现确定了 CXCR7 在血管功能障碍中的一个迄今为止尚未被认识到的作用，并证实了该受体是抗肿瘤治疗的一个合理靶点。
