Hua Fu, Tian Ye
Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University Suzhou 215004, China.
Department of Gynecology, Huai'an First People's Hospital, Nanjing Medical University Huai'an 223300, China.
Int J Clin Exp Pathol. 2017 Nov 1;10(11):11288-11299. eCollection 2017.
Chemokine (C-C motif) ligand 4 (CCL4) and vascular endothelial growth factor-A (VEGF-A) are involved in the progression and metastasis of some tumors, including ovarian cancer, colon cancer and prostate cancer. However, the roles of CCL4 and VEGF-A in human endometrial cancer (EC) are still unclear. Here, we demonstrated that the production of CCL4 and VEGF-A was significantly higher in EC tissues than in normal tissues, and their expression profiles were associated with the clinical stage of EC. In addition, we found that CCL4 promoted the angiogenesis and invasive ability of EC tumors by increasing the production of VEGF-A. We further confirmed the effect of CCL4 in the growth of EC tumors by silencing the expression of CCL4 in EC cell lines. Finally, we found that CCL4 upregulated VEGF-A expression by activating STAT3, and it enhanced the progression and metastasis of EC. Our study showed that CCL4 promoted tumor growth by upregulating VEGF-A expression, which affected the STAT3 signal pathway in the EC cells.
趋化因子（C-C基序）配体4（CCL4）和血管内皮生长因子-A（VEGF-A）参与包括卵巢癌、结肠癌和前列腺癌在内的某些肿瘤的进展和转移。然而，CCL4和VEGF-A在人类子宫内膜癌（EC）中的作用仍不清楚。在此，我们证明CCL4和VEGF-A在EC组织中的产生显著高于正常组织，且它们的表达谱与EC的临床分期相关。此外，我们发现CCL4通过增加VEGF-A的产生促进EC肿瘤的血管生成和侵袭能力。我们通过沉默EC细胞系中CCL4的表达进一步证实了CCL4对EC肿瘤生长的影响。最后，我们发现CCL4通过激活STAT3上调VEGF-A表达，并增强了EC的进展和转移。我们的研究表明，CCL4通过上调VEGF-A表达促进肿瘤生长，这影响了EC细胞中的STAT3信号通路。
