Abstract 96: Elucidating the role of CXCL17/GPR35 axis in breast cancer bone metastasis

Abstract Breast cancer (BC) has a high propensity to metastasize to the bone, but the molecular mechanisms driving bone metastasis (BoM) are not yet fully understood. BC cells establish bidirectional interactions with the bone microenvironment through altered expression of several chemokines and their receptors to facilitate metastasis and niche formation. Various G protein-coupled receptors are involved in oncogenic processes. Recently, it has been reported that G protein-coupled receptor 35 (GPR35), a cognate receptor for CXCL17, plays a significant role in tumor progression, metastasis, and drug resistance; however, its role in the modulation of bone microenvironment has not been elucidated. Here, we analyzed the expression of GPR35 in BC patients using the TCGA database. Furthermore, we also employed immunohistochemistry to examine the expression profile of GPR35 in BC tissue microarray. Our findings revealed high GPR35 expression in BC relative to the normal breast tissue. High GPR35 expression in BC also correlated positively with poor patient outcomes. Moreover, GPR35 expression was elevated in human as well as syngeneic BC bone metastatic cell lines (SCP2, SCP28, and E0771/Bone) compared to their relative parental cell lines (MDA-MB-231 and E0771P), advocating its significant potential in bone metastasis. Since most of the BC bone metastasis is osteolytic (bone destructive) in nature, and osteoblasts (OBs) regulate the osteoclasts (OCs) functions, therefore we examined the effect of conditioned media (CM) from the BC cells treated with either vehicle or rhCXCL17 on OBs and OCs. BC-CM induced bone cell differentiation, which was remarkably significant in OBs and OCs treated with BC-CM of rhCXCL17-treated cells. Together, these findings highlight the critical role of the CXCL17/GPR35 signaling axis in bone microenvironment remodeling supporting BC cell colonization. Citation Format: Gunjan Sharma, K. M. Abdullah, Seema Singh, Ajay P. Singh, Jawed A. Siddiqui. Elucidating the role of CXCL17/GPR35 axis in breast cancer bone metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 96.