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Abstract 111: The CX3CR1-Fractalkine axis drives both circulating prostate cancer cells and macrophages to the bone metastatic microenvironment
Journal article   Open access   Peer reviewed

Abstract 111: The CX3CR1-Fractalkine axis drives both circulating prostate cancer cells and macrophages to the bone metastatic microenvironment

Ramanpreet Kaur, Chen Qian, Joseph Salvino, Olimpia Meucci and Alessandro Fatatis
Cancer research (Chicago, Ill.), v 78(13_Supplement), pp 111-111
01 Jul 2018
DOI: https://doi.org/10.1158/1538-7445.AM2018-111
url
https://doi.org/10.1158/1538-7445.am2018-111View
Published, Version of Record (VoR)CC BY-NC V4.0,  Open

Abstract

Abstract Prostate cancer (PCa) is the second most frequently diagnosed cancer and its progression into metastatic disease reduces the 5-year survival rate to 29% in diagnosed men. A better understanding of the mechanisms underpinning metastatic dissemination and the role played by the tumor microenvironment at distant sites is essential. Our lab has shown that PCa cells express the chemokine receptor CX3CR1 and seed the skeleton when attracted by bone-derived Fractalkine (FKN) (a.k.a. CX3CL1). A crucial component of the bone microenvironment consists of heterogeneous populations of tumor-associated macrophages (TAMs), which can polarize into M1 or M2 phenotypes and are likely implicated in metastatic progression. TAMs migrate in close proximity of cancer cells and release growth factors, chemokines, and other inflammatory mediators that influence tumor growth. Using cell biology tools, we show that both PCa cells and macrophages express the CX3CR1 receptor, which signal to downstream targets when engaged by FKN and is inhibited by a novel small-molecule inhibitor. We also employed a mouse model of cancer cell dissemination and metastasis to show that our novel CX3CR1 antagonist impairs tumor seeding to the skeleton. Furthermore, as macrophages also express CX3CR1, targeting this receptor may potentially hinder TAMs' accumulation into the metastatic microenvironment, depriving it of crucial pro-metastatic conditioning. In conclusion, we propose that the CX3CR1-FKN axis drives both cancer cells and TAMs to metastatic sites and that the mitigation of the functional interactions between this receptor and its unique chemokine ligand by antagonists of CX3CR1 will impair the clinical progression of PCa metastasis. Citation Format: Ramanpreet Kaur, Chen Qian, Joseph Salvino, Olimpia Meucci, Alessandro Fatatis. The CX3CR1-Fractalkine axis drives both circulating prostate cancer cells and macrophages to the bone metastatic microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 111.

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Collaboration types
Domestic collaboration
Web of Science research areas
Oncology
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