Молекулярная и генетическая медицина

High-Expressed CXCR7 Contributes to CXCL12-Mediated Protection from Apoptosis in Lymphoma Cells

Abstract

Dongsheng Xu, Xiaobei Deng, Lisha Qiu, Xiaoxiao Qian, Yuqing Yan, Tong Lu and Jianguo Wu

Viral genes may act as oncogenes and interact with intracellular proteins, which are related to oncogenesis and tumor growth. Autocrining CXCL12 in growing tumor tissue plays critical roles in modulating cell proliferation and survival through its receptor CXCR4 and CXCR7. Recently, a number of research reports indicated that CXCR7 displays high expression in many kinds of tumor tissues and cell lines and that high -expressed CXCR7 may be involved in cell survival and migration. To date, CXCR7’s biological function and signaling in cancer pathogenesis is unclear. In this study, we first found there are higher expression of CXCR7 in both lymphocyte nodes and EBV positive lymphoma cell line IB4. The results further suggested that high-expressed CXCR7 plays a role in CXCL12 mediated anti-apoptosis and inhibition of CXCR7 through CXCR7 inhibitor CCX771 significantly attenuated the function of CXCL12 on anti-apoptosis. Furthermore, we observed that CXCR7 inhibitor directly reduced protection of endogenous CXCL12 from apoptosis in EBV positive lymphoma cell line. Finally, the results revealed that CXCL12 activated CXCR7 trafficking to membrane and interaction of CXCR7 and β-arrestin-2 during anti-apoptosis process. The study suggested that the high expressed CXCR7 may have effect on anti-apoptosis and inhibitor of CXCR7 may become potential target for cancer therapy.