Influence Of CCL18 From Tumor Associated Macrophages On Breast Cancer Angiogenesis

Objective: Angiogenesis is a key process in tumor growth and metastasis and is a major independent prognostic factor in breast cancer. In this study, we would investigate whether CCL18 released by TAMs could promote angiogenesis of breast carcer, and be a potential therapeutic target to block the angiogenesis of breast cancer.Methods: Clinical cases of breast invasive ductal carcinoma, including age, tumor size, degree of differentiation, lymphatic metastasis, ER, and so on. Immunohistochemical staining for CCL18 and CD34 is applied to breast tissue section from patients with breast carcinoma. Then the relationship between intratumoral TAMs and MVD counts is determined. The model of TAMs is established with Activating macrophages, induced by IL-4 or breast cancer cells coculturing, and then to detect the secretion of CCL18 by ELISA. In addition, Chicken chorioallantoic membrane (CAM) assay is used to evaluate the effect of CCL18 on agiogenesis in vivo.Results: Immunohistochemistry for CD34 and CCL18 expression in breast cancer tissues reveals that in areas with a high CCL18+ TAM count, the MVD count is high, implying that CCL18 may promote angiogenesis in breast cancer. The number of CCL18+ TAM, relates to tumor size, stage, degree of differentiation, lymphatic metastasis and distant metastasis. The results of ELISA shows that the supernatant of activating macrophages, induced by IL-4 or breast cancer cells coculturing, would have high expression of CCL18. The results of CAM assay also show that CCL18 has angiogenic effect as well as VEGF.Conclusion: CCL18 released by TAMs could promote angiogenesis of breast carcer, and be a potential therapeutic target to block the angiogenesis of breast cancer.