Abstract 3142: Expression of C-X-C motif chemokine 10 (CXCL10) in breast cancer

Abstract

Abstract Chemokines are small cytokine-like secreted proteins with chemoattractant properties which function in the recruitment of leucocytes into inflamed tissue. Besides well studied roles in the immune system, chemokines and their receptors have also been shown to play critical roles in tumorigenesis. The present study focuses on C-X-C motif chemokine 10 (CXCL10), a potent chemoattractant for stimulated T-cells and NK-cells. Both CXCL10 and its receptor CXCR3 are expressed by breast tumor cells, and accumulating data suggests roles for this chemokine and its receptor in breast cancer development and proliferation. We have previously shown CXCL10 to be significantly upregulated in ER positive as well as negative breast cancer cell lines over-expressing 17β hydroxysteroid dehydrogenase 14 (17βHSD14). Using a validated anti-CXCL10 primary antibody, we examined the relationship between CXCL10 expression and clinicopathological features in tissue microarrays comprised of tumor material from 912 breast cancer patients participating in a randomized tamoxifen trial conducted in Stockholm, Sweden, 1976-1990. All patients had lymph node negative primary breast cancer and were postmenopausal at the time of diagnosis. Results were obtained from tumors of 793 patients, of which 6% were deemed negative, 23% weak, 28% moderate, and 42% strong. Staining intensity of CXCL10 was strongly correlated with expression of 17βHSD14 (p<0.0001), however no significant correlation was observed between CXCL10 and prognostic markers such as ER, PR or tumor size. No clear associations between CXCL10-expression levels and the clinical outcome of tamoxifen treatment were observed, and moreover no prognostic value of CXCL10 was seen in systemically untreated patients. In the present study we have investigated expression of CXCL10 in a breast tumour cohort. We have previously found a functional relationship between 17βHSD14 and CXCL10 suggesting a possible regulatory loop involving this 17βHSD enzyme. A strong association between CXCL10 and 17βHSD14 in this tumor cohort further strengthens this theory. We found CXCL10 to be ubiquitously expressed in the tumors however no significant relationship between CXCL10 expression and tamoxifen treatment prediction or prognosis among patients was noted. Previous data on the action of CXCL10 in cancer is conflicting as the chemokine has been suggested to act as a growth promoter as well as an inhibitor growth. The presence of two splice variants of the CXCL10 receptor CXCR3, of which CXCR3-A has been shown to promote proliferation and CXCR3-B- to induce apoptosis, has generally not been accounted for, and varying expression levels of these receptors may to some degree explain these conflicting findings. In order to elucidate the role of CXCL10 in breast cancer, tumoral distribution and expression levels of these two splice variants of the CXCL10 receptor need to be evaluated. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3142. doi:10.1158/1538-7445.AM2011-3142