Volume 2 • Issue 3 • 1000120 J Carcinogene Mutagene ISSN:2157-2518 JCM, an open access journal Research Article Open Access Razmkhah et al., J Carcinogene Mutagene 2011, 2:3 DOI: 4172/2157-2518.1000120 Research Article Open Access Chemokines and Chemokine Receptors Expression in the Adipose Derived Stem Cells (ASCs), Breast Tissues and in Peripheral Blood of Patients with Breast Cancer Mahboobeh Razmkhah 1 , Mansooreh Jaberipour 1 and Abbas Ghaderi 1,2 * 1 Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran 2 Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran *Corresponding author: Abbas Ghaderi, Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences, PO BOX: 71345-1798, Shiraz-Iran, Fax: 0098 711 230 4952; Tel: 0098 711 230 3687; E-mail: ghaderia@sums.ac.ir Received June 01, 2011; Accepted September 26, 2011; Published September 29, 2011 Citation: Razmkhah M, Jaberipour M, Ghaderi A (2011) Chemokines and Chemokine Receptors Expression in the Adipose Derived Stem Cells (ASCs), Breast Tissues and in Peripheral Blood of Patients with Breast Cancer. J Carcinogene Mutagene 2:120. doi:10.4172/2157-2518.1000120 Copyright: © 2011 Razmkhah M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract It has been demonstrated that the tumor angiogenic ability is one of the most important predictors of breast cancer progression. Factors controlling tumor angiogenesis are varied and currently under investigation. Chemokines, which produced by both tumor cells and cells of tumor microenvironment are known with a role in tumor angiogenesis. Here, we examined the expressions of SDF-1/CXCR4/CXCR7, CXCL13/CXCR5, RANTES/ CCR5, MCP-1 and CCR7 in adipose derived stem cells (ASCs) and breast cancer tissues of breast cancer patients. Results of ASCs were compared to those from sex matched healthy individuals. Data of breast cancer tissues were compared between stage III and stages I and II tumors. As a result, SDF-1 protein showed higher expression in ASCs from patients with pathological stage III compared to those with pathological stages I and II tumors and normal individuals. In breast cancer tissues, the mRNA expressions of MCP-1 and SDF-1 were 8.4 and 2.6-fold more in patients with stage III than those with stages I and II tumors. RANTES and CXCR4 mRNAs had signifcantly more expression in tissues of HER2 + compared to HER2 - patients (P value = 0.01 and 0.04, respectively). Current information suggest adipose derived stem cells as one of the major players of breast cancer microenvironment which express angiogenic chemokine molecules and contribute to the breast cancer cells growth and progression. Keywords: Breast cancer; Angiogenesis; ASCs; Chemokines; Tumor microenvironment Introduction Although most patients with solid tumors, including breast cancer, undergo primary surgery, they are still at considerable risk of dying from metastases to other organs [1]. During the past decade much work has been devoted to the search for predictors of tumor formation and markers of metastasis in peripheral blood. Recently, it has been demonstrated that the tumor’s angiogenic capacity is one of the important features of breast cancer progression [2]. Recently, the importance of chemokines and chemokine receptors in tumorigenesis has been defned. Tey closely correlate with tumor cell proliferation, angiogenesis and metastasis. Te stromal cell derived factor-1 (SDF-1)/CXCR4/CXCR7 axis plays important roles in the recruitment of endothelial progenitor cells, angiogenesis [3,4], and metastasis of diferent types of tumors [4-6]. Tere are several investigations explaining the expressions of chemokine and chemokine receptors in breast cancer tissues and their roles in breast cancer growth and metastasis. Te most popular report linking the expressions of chemokine/chemokine receptors specially SDF-1/ CXCR4 to breast cancer metastasis has been published by Muller et al. [7]. Tey succeeded to inhibit the breast cancer metastasis using a CXCR4 neutralizing antibody [7]. Moreover, CXCR4 may contribute to the production of angiogenic factors such as interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF) by tumor cells [8]. Trough angiogenesis, regulated upon activation, normal T cell expressed and secreted (RANTES) and monocyte chemotactic protein (MCP)-1 has also been reported to have tumor promoting efects [9]. In contrast, the interferon-gamma-inducible protein 10 (IP-10)/ CXCR3 axis has angiostatic efects and may suppress tumor growth and progression [3]. In this connection, IP-10 activation was found to suppress the growth and recurrence of endometrial cancer [10]. In addition, the expressions of both CXCR3 and IP-10 has been shown in human breast tumors and the expression level of CXCR3 in breast tumor samples was shown to be a predictor of poor prognosis for this type of cancer [11]. It has increasingly been shown that chemokines are produced by tumor cells as well as by cells of the tumor microenvironment such as cancer-associated fbroblasts (CAFs) and mesenchymal stem cells (MSCs) [12,13]. Cancer stem cells can arise from mesenchymal stem cells (MSCs) recruited to the tumor microenvironment, as shown in the development of epithelial cancers [14]. Experiments in animal models showed that MSCs are able to migrate to tumor and injury sites afer intravenous (i.v.) injection [15]. Tis property is strongly depends on the expressions of several chemokine receptors, especially CXCR4 on MSCs [16]. Tese cells may contribute to the cancer progression through several mechanisms, among which the production of proangiogenic factors such as VEGF and IL-6 [17], and also matrix- degrading enzymes such as matrix metalloproteinases (MMPs) [18] are of particular interest. Tus, MSCs might be predicted to promote, rather than inhibit, tumor growth [19]. Mesenchymal stem cells can be isolated from embryonic or adult tissues such as bone marrow and adipose tissue [20]. Adipose-derived stem cells (ASCs) have a high J o u r n a l o f C a r ci n o g e n es i s & M u t a g e n e s i s ISSN: 2157-2518 Journal of Carcinogenesis & Mutagenesis