Abstract 655: Racial difference in CXC motif chemokine receptor 4 expression in prostate cancer

Abstract

Abstract Prostate cancer incidence and mortality rates are remarkably higher in African-American (AA) men as compared to the Caucasian-American (CA) counterparts. Despite these recognitions, precise causes underlying such prevalent racial disparities remain poorly understood. Understandably, socioeconomic factors accounts for such differences, whoever the molecular basis of this disparity is now being increasingly realized. The stromal microenvironment has emerged as a key player in the development and progression of cancer regulating the inflammatory signaling pathways. In our recently published study (Clin. Cancer Res. 26:1915-1923, 2020) we have demonstrated the role of stroma in driving aggressiveness in AA prostate cancer patients prognostic of tumor recurrence. In stromal compartment, the altered genes predominantly linked with cytokine signaling molecules are associated with immune response, cytokine signaling, chemotaxis, and tumor-immunobiology. Chemokines and their receptors, particularly chemokine (C-X-C motif) ligand 12 (CXCL12) and its receptor chemokine (C-X-C motif) receptor 4 (CXCR4), have gained attention for their functional roles in the development and maintenance of the hematopoietic and immune systems, as well as in cancer metastasis and progression. CXCR4 has been demonstrated to be upregulated in a variety of different cancer cell lines and in various human cancers including breast, prostate, ovarian, lung, and gastric cancer. CXCR4 directs the migration, invasion and dissemination of tumor cells to specific sites that are rich in CXCL12, including lymph nodes, bone, the lungs and body organs. We investigated whether there is an association between CXCR4 expression and prognosis related to racial disparity and prostate cancer. Fresh frozen and paraffin-embedded sections were obtained pot-surgery and expression of CXCR4 and its associated molecules were determined in both AA and CA specimens. Western blotting was performed for CXCR4, IL-6 and MMP9 and CK18 as epithelial loading control in prostate cancer AA men and matched Gleason score from CA men of Gleason score 6-8. A marked increase in the expression of CXCR4, IL6 and MMP9 were noted in AA-prostate cancer specimens compared to CA tumors. We also evaluated the pathological grade, metastasis, and patient prognosis. CXCR4 staining was moderate to strong in the prostate cancer from AA men compared to CA men with moderate to weak expression which positively associated with tumor progression. These observations are consistent with the evidence that the tumor-adjacent stroma heavily influences prostate cancer aggressiveness in AA patients which is different from the CA men. We suggest CXCR4 as a useful prognostic factor and stroma-associated biomarker for racial disparities of prostate cancer. Citation Format: Eswar Shankar, Gregory T. MacLennan, Sanjay Gupta. Racial difference in CXC motif chemokine receptor 4 expression in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 655.