Role of CCL5 in invasion, proliferation and proportion of CD44+/CD24− phenotype of MCF-7 cells and correlation of CCL5 and CCR5 expression with breast cancer progression

Abstract

Abstract. This study was undertaken to observe the effects and possible mechanism of CC chemokine ligand 5 (CCL5) on invasion, proliferation and percentage of CD44 + /CD24 IntroductionBreast cancer is a leading cause of death for women in many countries. The ability of breast cancer cells to metastasize to distal organs makes this disease refractory and incurable and is the vital factor contributing to the therapeutic effect and prognosis of breast cancer (1). The metastasis of cancer consisting of a series of complex steps is influenced and regulated by various factors in the microenvironment (2-5). Chemokines are small soluble molecules that are best known for their potent abilities to induce cellular migration, particularly by leukocytes during inflammation. It is widely accepted that a functional relationship exists between inflammation and cancer. Although inflammatory cells and cytokines may contribute to the host anti-tumor response, inflammation likely promotes tumor growth and progression as well (6). Prolonged inflammation is thought to potentiate carcinogenesis by providing a microenvironment that is ideal for cancer development and growth (6,7). Many cancer cells, including breast cancer cells, express chemokines and chemokine receptors (7). In addition to inducing inflammatory cell infiltration into the tumor, local chemokines may also mediate angiogenesis, serve as growth or survival factors, and regulate tumor cell migration or metastasis (8).CC chemokine ligand 5 (CCL5), originally identified as a product of activated T cells, is capable of recruiting T cells to inflammatory sites (9). Recent studies have shown that local production of CCL5, a potent chemotactic factor for inflammatory cells, is important in the progression of breast ONCOLOGY REPORTS

Beyond Cell Motility: The Expanding Roles of Chemokines and Their Receptors in Malignancy

“…Parallel studies on CCL5 demonstrated its ability to induce small increases in breast tumor cell proliferation; in one of the research systems, such CCL5 activity was mediated by CCR5dependent mTOR activation (46)(47)(48). CCR5, a major CCL5 receptor, was targeted in several studies by maraviroc, leading to controversial results in terms of tumor cell proliferation (48)(49)(50)(51), which possibly reflect the use of different model systems and/or the ability of CCL5 to activate CCR1 and CCR3 in addition to CCR5.…”

“…The two inflammatory CC chemokines, CCL2 and CCL5 were also found to elevate the generation of CSCs. This was evidenced by a CCL2-promoted formation of primary and secondary tumor spheroids that contained more self-renewing CSCs (82), and by the fact that stimulation of breast tumor cells with CCL5 increased the CD44 + /CD24 − sub-population (47). These CCL5-enriched CSCs expressed higher levels of the corresponding receptor CCR5 and were able to invade more than non-CSCs, ability that was abrogated by inhibition of CCR5 (47).…”

“…This was evidenced by a CCL2-promoted formation of primary and secondary tumor spheroids that contained more self-renewing CSCs (82), and by the fact that stimulation of breast tumor cells with CCL5 increased the CD44 + /CD24 − sub-population (47). These CCL5-enriched CSCs expressed higher levels of the corresponding receptor CCR5 and were able to invade more than non-CSCs, ability that was abrogated by inhibition of CCR5 (47). In another study, CCR5-expressing breast cancer cells demonstrated higher potency in forming mammospheres in vitro and in initiating tumor formation in vivo, than cells not expressing the receptor (83).…”

The Role of Adipose-derived Stem Cell in Breast Reconstruction with Fat Grafting: A Literature Review

“…Adipokines play a role in increasing the invasion of human and mouse breast cancer cells characterized by excessive expression of proteases, including proinflammatory cytokines (IL-6, IL-1β) and MMP-11 when co-cultured with adipocytes. Research shows that ADSCs increase the motility of MCF-7 breast cancer cells in vitro through the secretion of the chemokine CCL5 [13].…”

CXCL1/CXCR2 and CCL5/CCR1/CCR5 Promote Radiation-Induced Reprogramming of Breast Non-cancer Stem Cells into Cancer Stem Cells and Predict Patient Clinical Outcome

“…Concurrently, multiple studies have established a connection between inflammation and cancer stem cells, with a particular emphasis on cytokines and chemokines. Treatment of breast cancer cell lines with Chemokine (C-C motif) ligand 5 (CCL5) leads to an enrichment of CD44 high /CD24l ow/-CSCs [10]. Chen et al identified CCL20 as an inflammatory factor that increases both ALDH+ and CD44 high /CD24l ow/-breast CSC frequencies in a population treated with taxanes [11].…”