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Elevated Expression of the CC Chemokine Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) in Advanced Breast Carcinoma¹

Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv 69978 [G. L., S. S., I. K., A. B-B.]; Department of Surgery A, Tel-Aviv Sourasky Medical Center, Tel-Aviv 64239 [O. K.]; Department of Pathology, Ramat Marpe Hospital, Ramat Gan 49631 [S. E., D. N.]; Institute of Pathology, Diagnostic and Research Cancer Center, Tel-Aviv Sourasky Medical Center, Tel-Aviv 64239 [B. L-M.]; and Department of Oncology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978 [S. C.], Israel

Breast carcinoma is the most common malignant disease among women and the second most lethal one. In search for a better understanding of the role of cellular mediators in the progression of this disease, we investigated the potential involvement of the CC chemokine Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) in breast carcinoma progression. To this end, RANTES expression was determined in breast tumor cell lines and in sections of breast carcinomas, followed by analysis of the incidence and intensity of its expression in different stages of the disease. Our study reveals that high and physiologically relevant levels of RANTES are constitutively produced by T47D and MCF-7 breast tumor cell lines. Analysis of RANTES expression in sections of breast carcinomas demonstrates a high incidence of RANTES expression in epithelial tumor cells; the chemokine was expressed in 74% of the sections. RANTES expression was rarely detected in normal duct epithelial cells or in epithelial cells that constitute benign breast lumps, which were located in proximity to tumor cells. High incidence and intensity of RANTES expression were detected in sections of most of the patients with stage II and stage III of the disease (expression was detected in 83 and 83.3%, respectively), whereas RANTES was expressed at a lower incidence and intensity in sections of patients with stage I of breast carcinoma (55% of the cases). Most importantly, the expression of RANTES was minimally detected in sections of patients diagnosed with benign breast disorders and of women that underwent reduction mammoplasty (15.4% of the cases). These results indicate that the expression of RANTES is directly correlated with a more advanced stage of disease, suggesting that RANTES may be involved in breast cancer progression. Moreover, it is possible that in patients diagnosed with benign breast disorders, RANTES expression may be indicative of an ongoing, but as yet undetectable, malignant process.

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