Monterrubio María, Mellado Mario, Carrera Ana C, Rodríguez-Frade José Miguel
Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Campus de Cantoblanco, E-28049 Madrid, Spain.
Biochem Biophys Res Commun. 2009 Oct 16;388(2):199-204. doi: 10.1016/j.bbrc.2009.07.153. Epub 2009 Aug 4.
Tumor dissemination is a complex process, in which certain steps resemble those in leukocyte homing. Specific chemokine/chemokine receptor pairs have important roles in both processes. CXCL12/CXCR4 is the most commonly expressed chemokine/chemokine receptor pair in human cancers, in which it regulates cell adhesion, extravasation, metastatic colonization, angiogenesis, and proliferation. All of these processes require activation of signaling pathways that include G proteins, phosphatidylinositol-3 kinase (PI3K), JAK kinases, Rho GTPases, and focal adhesion-associated proteins. We analyzed these pathways in a human melanoma cell line in response to CXCL12 stimulation, and found that PI3Kgamma regulates tumor cell adhesion through mechanisms different from those involved in cell invasion. Our data indicate that, following CXCR4 activation after CXCL12 binding, the invasion and adhesion processes are regulated differently by distinct downstream events in these signaling cascades.
肿瘤播散是一个复杂的过程，其中某些步骤类似于白细胞归巢中的步骤。特定的趋化因子/趋化因子受体对在这两个过程中都起着重要作用。CXCL12/CXCR4是人类癌症中最常表达的趋化因子/趋化因子受体对，它在其中调节细胞黏附、外渗、转移定植、血管生成和增殖。所有这些过程都需要激活包括G蛋白、磷脂酰肌醇-3激酶（PI3K）、JAK激酶、Rho GTP酶和黏着斑相关蛋白在内的信号通路。我们分析了人类黑色素瘤细胞系中这些通路对CXCL12刺激的反应，发现PI3Kγ通过与细胞侵袭不同的机制调节肿瘤细胞黏附。我们的数据表明，在CXCL12结合后CXCR4激活后，这些信号级联中的不同下游事件对侵袭和黏附过程的调节方式不同。
