Expression of CCL5/RANTES by Hodgkin and Reed‐Sternberg cells and its possible role in the recruitment of mast cells into lymphomatous tissue

Kim

et al. 2013

Cell Mol Immunol

Breast cancer (BC) is a leading cause of mortality among women in the world. To date, a number of molecules have been established as disease status indicators and therapeutic targets. The best known among them are estrogen receptor-a (ER-a), progesterone receptor (PR) and HER-2/neu. About 15%-20% BC patients do not respond effectively to therapies targeting these classes of tumor-promoting factors. Thus, additional targets are strongly and urgently sought after in therapy for human BCs negative for ER, PR and HER-2, the so-called triple-negative BC (TNBC). Recent clinical work has revealed that CC chemokine ligand 5 (CCL5) is strongly associated with the progression of BC, particularly TNBC. How CCL5 contributes to the development of TNBC is not well understood. Experimental animal studies have begun to address the mechanistic issue. In this article, we will review the clinical and laboratory work in this area that has led to our own hypothesis that targeting CCL5 in TNBCs will have favorable therapeutic outcomes with minimal adverse impact on the general physiology.

Section: Ccl5 and Other Cancersmentioning

confidence: 99%

CCL5 as a potential immunotherapeutic target in triple-negative breast cancer

Kim

et al. 2013

Cell Mol Immunol

“…CCL5, a classical pro-inflammatory chemokine, has been found in several cancers as a promalignant factor (33,34). As for breast cancer, previous studies have showed that local production of CCL5 is important in the progression of breast cancer and that more advanced stages of breast cancer correlated with higher levels of CCL5 expression (8,10), but its precise function and mechanism have not been clearly clarified.…”

Section: Discussionmentioning

confidence: 99%

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

Feng²,

Yao³

et al. 2009

Oncol Rep

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

“…PBMCs were resuspended in complete medium at a final concentration of 3.0x10 6 /ml. The CD4 + T cells were isolated from PBMC using anti CD4 + conjugated immunomagnetic microbeads (Miltenyi Biotec, Bergisch Gladbach, Germany) according to the manufacturer's instructions and described by Fischer (7,8).…”

Section: Peripheral Blood Mononuclear Cell Preparation and Purificatimentioning

confidence: 99%

“…The migration of human in vitro-developed CD4 + T cells was tested using a modified 24-well Boyden chamber (Neuroprobe, Cabin John, MD, USA) as previously described by Fischer et al (7,8). Nitrocellulose filters (Millipore/Continental Water Systems, Bedford, MA, USA) with a pore size of 8 µm were coated with human plasma …”

Section: Peripheral Blood Mononuclear Cell Preparation and Purificatimentioning

confidence: 99%

“…Buri et al found that CCL5 was only expressed in the infiltrated non-neoplastic leukocytes of CHL but not in HRS cells (6). However, subsequent studies demonstrated the expression of CCL5 in HRS cells and its potential role in the recruitment of inflammatory cells into lymphoma tissue (7,8). Emmerich et al found that NF-кB transcription factor iкBα is overexpressed in RS cells (9).…”

Section: Introductionmentioning

confidence: 99%

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Analysis of CCL5 expression in classical Hodgkin's lymphoma L428 cell line

Liu

et al. 2011

Mol Med Report

Abstract. CCL5 is one of the chemoattractant cytokines involved in inflammatory observed in both diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin's lymphoma (CHL). However, the pathological effects of CCL5 remain unclear. To gain a better understanding of the role of CCL5 in CHL and DLBCL, we examined the expression of CCL5 in the CHL cell line L428 and the DLBCL cell lines Ly1 and Ly8, as well as its chemotactic effect on CD4 + T cells. CCL5 mRNA expression was detected by real-time quantitative RT-PCR. Intracellular CCL5 protein expression was analyzed using confocal microscopy, and CCL5 protein secretion was detected by ELISA. The chemotactic function of CCL5 was assessed using a Transwell coculture system, and the number of migrated CD4 + T cells was counted. Moreover, the p-iкBα and p65 levels of NF-кB signaling molecules in these lymphoma cell lines were detected by Western blotting. The results showed that CCL5 mRNA and protein expression in the L428 cells was significantly higher than in Ly1 and Ly8 cells (p<0.05). L428 cells secreted more CCL5 than the Ly1 or Ly8 cells, and the secreted CCL5 was capable of inducing CD4 + T cell migration. The expression levels of the NF-кB transcription factors p65 and p-iкBα were examined in these lymphoma cells. L428, Ly1 and Ly8 cells expressed similar levels of p65, while p-iкBα expression was higher in the L428 cells than in the Ly1 or Ly8 cells, indicating that a high CCL5 expression may be related to the increased activity of the NF-кB signaling pathway in L428 cells.