Effect Of Chemerin On Proliferation And Migration Of Breast Cancer And Its Molecular Mechanism

Background Breast cancer is a heterogeneous disease with the highest incidence of cancer in Chinese women.However,there are still many unknowns about the pathogenic factors of breast cancer.The study found that there was a strong relationship between obesity and breast cancer.Chemerin is a newly identified adipokine in recent years.It has been proved to play an important biological role in the pathophysiological process of various malignant tumors,such as liver cancer,non-small cell lung cancer,melanoma and so on.And does chemerin play a role in the occurrence and development of breast cancer? What is molecular mechanism of it? Objective There is no clear report at present.The purpose of this study was to investigate the expression of chemerin in breast cancer mice and its effect on the proliferation and migration of breast cancer cells,and to explore the mechanism of chemerin in the pathophysiological process of breast cancer.Methods Mouse breast cancer 4T1 cells were inoculated into Balb/c mice to establish a breast cancer model.The expression of chemerin protein in peripheral blood and breast tissues of tumor-bearing mice was detected by ELISA and Western blot,respectively.The relationship between the expression of chemerin protein and breast cancer was analyzed.Human Breast Cancer Cell Lines MCF-7 and MDA-MB-231 were treated with three different concentrations of chemerin recombinant protein and 100 μg/L chemerin neutralizing antibody,respectively.The effects of chemerin on the proliferation and migration of cancer cells were detected by MTT and scratch test,respectively.After treated with 100μg/L chemerin recombinant protein and 100μg/L chemerin neutralizing antibody,phosphorylation proteins in three signaling pathways,JNK,ERK1/2 and p38,were detected in breast cancer cells MCF-7 and MDA-MB-231 by Western Blot.Human breast cancer cells MCF-7 and MDA-MB-231 were pretreated with chemerin recombinant protein（100μg/L）,and then treated with JNK,ERK1/2 and p38 signal pathway inhibitor respectively.The effect of chemerin on the migration of breast cancer cells was detected by scratch test.Results Compared with normal mice,the expressions of chemerin protein in peripheral blood and mammary gland of tumor-bearing mice were significantly increased（p<0.05）.The scratch mobility and MTT absorbance（OD）value of breast cancer cells treated with recombinant.chemerin protein significantly increased with the increase of protein concentration（p<0.05）.The scratch migration rate and MTT absorbance（OD）value of breast cancer cells treated with chemerin neutralizing antibody significantly decreased（p<0.05）.After treated with chemerin recombinant protein,the phosphorylation degree of JNK and ERK1/2 signaling pathway proteins in cells increased significantly（p<0.05）,but the phosphorylation degree of p38 signaling pathway protein did not change significantly.After treated with chemerin neutralizing antibody,the phosphorylation degree of JNK and ERK1/2signaling pathway proteins in cells decreased significantly（p<0.05）,but the phosphorylation degree of p38 signaling pathway protein did not change significantly.After treated with JNK and ERK1/2 signaling pathway inhibitor,the scratch migration rate of breast cancer cells decreased significantly（p<0.05）,while scratch migration rate did not change significantly trested with p38 signaling pathway inhibitor.Conclusions Chemerin protein expresses high in both breast cancer tissues and peripheral blood of tumor-bearing mice.It can promote the proliferation and migration of breast cancer cells in a concentration gradient manner within a certain range.And its biological effect can be exerted in occurrence and development of breast cancer through two signaling pathways of JNK and ERK1/2.