Roles of integrin αvβ3 in interleukin-8-mediated metastasis and angiogenesis of estrogen receptor negative breast cancer cells

Abstract

Objective To identify the role of integin αvβ3 in interleukin (IL)-8-mediated metastasis and angiogenesis of breast cancer cells.Methods IL-8 and neutralizing antibody of integrin αvβ3 were used in invasion and human umbilical vein endothelial cells (HUVECs)-tumor cells adhesion assay to observe the changes of metastasis of breast cancer cells.Proliferation assay and angiogenesis of HUVECs cultured with IL-8 and antibody of αvβ3 were applied to evaluate the effect of αvβ3 on IL-8-mediated angiogenesis.The correlation between IL-8 and αvβ3 expression was examined by using immunohistochemistry,and relationship between the expression of IL-8 and αvβ3 with estrogen receptor (ER) status in patients was further analyzed.Results IL-8 significantly inhanced the migration of ER negative breast cancer cell lines BT-549 and MDA-MB-231 as compared with those cultured with phosphate buffer (PBS,P＜0.05).After the addition of antibody of αvβ3,the number of BT-549 and MDA-MB-231 cells cultured with IL-8 was declined significantly (P ＜0.01),whereas IL-8 had no effect on ER positive breast cancer cell line MCF-7 (P ＞ 0.05).Proliferation of HUVECs cultured with IL-8 was markedly promoted (P ＜0.01),which could be blocked by antibody of αvβ3 (P ＜0.01).HUVECs cultured with IL-8 tended to form more microangioid structure,and suppression of angiogenesis could be observed after the addition of antibody of αvβ3.In the 104 breast cancer specimens,62.1％ showed positive αvβ3 expression in the IL-8 positive group,which was significantly higher than that in IL-8 negative group (P ＜ 0.01).In addition,the expression of αvβ3 was correlated with IL-8 in ER-negative breast cancer cells (P ＜ 0.05).Conclusion Integrin αvβ3 may be involved in metastasis and angiogenesis of ER-negative breast cancer cells promoted by IL-8.The expression of αvβ3 correlates with IL-8 expression,which is related to ER status. Key words: Breast neoplasms; Estrogen receptor; Interleukin-8 ; Integrin