Correlation Between The Expression Of CCL5,CCR5, MMP-9 In Breast Cancer And Clinical Pathological Features

Breast cancer is one of the most common malignant tumors. Despite modern improvements in the treatment of breast cancer including comprehensive therapeutic methods, have showed promising, the mortality is still very low. The invasion and metastasis are the main factors influencing the survival rate and mortality of breast cancer, therefore, invasion and metastasis of breast cancer have been the focus of both clinical and experimental research. Breast cancer cells mainly spread through blood vessels and lymph vessels, and tends to metastasize to axillary lymph nodes, bone, lung and liver, but rarely to skin and kidney. Several mechanisms may be responsible for the organ-specific metastasis of breast cancer. Among these mechanisms, homing theory was widely accepted. The homing theory illustrates that the target organs could release some chemokines; these chemokines could recruit cancer cells which express the corresponding chemokine receptors, promote the proliferation of these cells, and finally course organ-specific metastasis.CCL5 is a chemokine, which is also called RANTES (regulated upon activation normal T cell expressed and secreted). Various types of inflammatory cells such as NK cells and T cells can secrete CCL5. The receptors of CCL5 include CCR1, CCR3, CCR4 and CCR5, among which CCR1 and CCR5 are high affinity receptors. CCR5 is mainly expressed in white blood cells (such as T cells and mononuclear cells), microglia and promyelocyte. Specific ligands of CCR5 include CCL5,MIP-1?a,MIP-1?.Breast cancer cells can express and secrete CCL5 and CCR5. The levels of CCL5 and CCR5 are positively relevant to the grade and progress of breast cancer. CCL5 in tumors could promote tumor metastasis through recruiting and activating mononuclear cells and tumor cells, and promoting the expression of MMPs (matrix metalloproteinases). CCL5 could also promote the progress of tumor by autocrine and paracrine mechanism. MMP-9 is an enzyme which can degrade components of the extracellular matrix, facilitate invasion and metastasis of breast cancer cells and promote angiogenesis. MMP9 may play a pivotal role in metastasis of breast cancer.Therefore, it is of significance to explore the expression of CCL5, CCR5 and MMP-9, and further illuminate their role in the occurrence, development and treatment of breast cancer.Objective:To detect the expression of CCL5, CCR5 and MMP-9 in breast cancer and illuminate their relationship with clinical pathological parameters.Methods:70 samples were collected from Department of Breast & Thyroid Surgery, from January 1,2011 to August 31,2011. Pathology results of all specimen were breast invasive ductal carcinoma. All samples have not received chemotherapy or radiation treatment. According to AJCC (American Joint Committee on Cancer,2002), there were 20 cases (stage I),18 cases (stage II),32 cases (stage?). CCR5 and MMP-9 protein in 70 specimens of breast cancer and 70 normal breast tissues were detected by immunohistochemistry. The serum levels of CCL5 were measured by enzyme-linked immunosorbent assay (ELISA) based on serum extracted from 70 breast cancer patients and 50 healthy controls,and their clinical pathological significance analysis. The expression of CCL5/CCR5 were detected in breast cancer patients and the correlations of CCL5/CCR5 with prognosis were analyzed. The mRNA and protein expression of CCR5 in 2 human breast tumor cell lines were assayed by RT-PCR and Western Blot, respectively. This study was to investigate the expression differences of CCR5 in breast cancer cell lines in the cellular and molecular level.Results:1. The positive expression rate of CCR5 in breast cancer and normal mammary tissues were 74.43%,4.29%. The positive expression rate of MMP-9 in breast cancer and normal mammary tissues were 58.57%,17.14%.The difference between them was very significant (P<0.01).2. CCR5 and MMP-9 protein have no correlation with age of onset, menostasia and ER, PR, P53, Ki67. But CCR5 and MMP-9 were significantly correlated with maximum diameter of tumor, lymphatic metastasis and clinical stage (P<0.05). CCR5 was also correlated with HER2.3. Serum concentration of CCL5 had a remarkable correlation with lymph node metastasis of mammary cancer and clinical stage; however it had no correlation with other clinical indicators.4. There were correlation between the expression of CCL5, CCR5 and MMP-9 in breast cancer.5. Two human breast tumor cell lines expressed CCR5 and MDA-MB-453 cell line expressed more CCR5 than MCF-7 cell lines.6. The high expression of CCL5 and CCR5 may indicate poor prognosis.Conclusion:1. The expression of CCL5, CCR5 and MMP-9 in tissue and serum of breast cancer patients had correlation with the clinical stage and axillary lymph node metastasis. CCL5/CCR5 biological axis may be involved in lymph node metastasis by activating MMP-9.2. CCL5, CCR5 and MMP-9 could be a triple-biomarker for predicting infiltration and lymph node metastasis of breast cancer.