Abstract 1010: CCL5 in breast cancer: Circulating systemic levels and gene expression in the primary tumor microenvironment
Authors: Dwyer Roisin M. , Hartmann Marion C. , Costello Maria , Kerin Michael J. 
Published: February 2011

Abstract
CCL5/RANTES is a chemotactic cytokine which plays an important role in inflammation. There have also been conflicting reports of a potential role for this chemokine in breast cancer progression. The aim of this study was to determine circulating and tissue levels of CCL5 in breast cancer patients, and investigate a potential relationship with TGFβ1. Correlation of the chemokine with circulating hormone levels was also determined. Serum levels of CCL5 were quantified using ELISA in samples from breast cancer patients (n=110) and healthy controls (n=69). For gene expression analysis, tumor tissue samples (n=44) were available on a subset of the same breast cancer patients. Tissue harvested at reduction mammoplasty served as controls (n=16). RQ PCR was carried out using primers and probes targeting CCL5 and its principal receptor CCR5, as well as TGFβ1 and TGFβ Receptor II (TGFβRII). All data was correlated with patient clinicopathological characteristics. Investigation of a link between circulating hormones (FSH, LH, Estradiol and Progesterone) and CCL5 was also performed in healthy premenopausal volunteers (n=32). Within the breast cancer cohort, patients with the more invasive Basal epithelial subtype had significantly higher circulating CCL5 (77.72 ± 20.52ng/ml) than those with Luminal A subtype (47.85 ± 3.77ng/ml, p&lt;0.01). Patients with node negative disease had significantly higher levels of CCL5 (61.49 ± 7.48ng/ml) than patients with ≤2 lymph nodes positive (40.96 ± 6.34ng/ml, p&lt;0.05). As the number of positive nodes increased, CCL5 increased and was significantly higher in patients with ≥10 nodes positive (67.5 ± 11.02ng/ml, p&lt;0.05). This trend has previously been associated with circulating TGFβ1, and further investigation revealed a significant positive correlation between circulating CCL5 and TGFβ1 (n=138, r =0.44, p&lt;0.0001). Gene expression analysis revealed significantly higher expression of both CCL5 and CCR5 in tumor compared to normal breast tissue (p&lt;0.05). There was also a significant positive correlation between expression of the ligand and its receptor in the tissue samples (n=60, r =0.46, p&lt;0.0001). TGFβ1 expression was significantly higher in tumor compared to normal tissue (p&lt;0.001), while there was no significant change in TGFβRII. There was a significant negative correlation between CCL5 and circulating Estradiol and Progesterone (r = −0.36, r = −0.39 respectively p&lt;0.05) in healthy premenopausal volunteers. The data presented provides evidence of a potentially important role for CCL5 in breast cancer progression. The link between circulating CCL5 levels and number of positive lymph nodes suggest a potentially protective effect in early stage breast cancer, which then switches to a tumor promoting role in later stage disease. This closely reflects patterns of expression of TGFβ1, which has a well recognised role in breast cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1010.