Abstract
Abstract 2567: CX3CR1 surface expression on metastatic prostate cancer cells is increased by the target organs and is associated with a distinct metabolic phenotype
Cancer research (Chicago, Ill.), v 85(8_Supplement_1), 2567
21 Apr 2025
Abstract
Studies from us and others have shown that the chemokine receptor CX3CR1 drives cancer cells to the skeleton, activates pro-survival signaling pathways and bears unique therapeutic potential. We have recently reported that the small subsets of prostate cancer cells that expose CX3CR1 on their surface (CX3CR1Surf+) are endowed with stemness features and behave as metastasis-initiating cells (MICs). Interestingly, their CX3CR1Surf- counterparts can re-express CX3CR1 on the cell surface while undergoing partial EMT, thus re-acquiring MIC features. This phenotypic plasticity can be temporally monitored in vitro, with cultures of 100% CX3CR1Surf- cells reaching a phenotypic equilibrium (5-7% of CX3CR1Surf+) in ∼ 8 days. However, when cells at phenotypic equilibrium are grafted in mice via systemic blood circulation, the resulting tumors in the skeleton and soft tissues show a dramatic increase in the CX3CR1Surf+ fraction. This suggests that the stroma of target organs promotes CX3CR1 plasticity, an effect not observed when the same cells are grafted subcutaneously. We also show that FX-68, a potent and specific antagonist of CX3CR1, dramatically reduces the number of disseminated tumors and total tumor burden in mice. FX-68 does not alter the percentage of CX3CR1Surf+ cancer cells in disseminated tumors, suggesting that its anti-tumor effects are exerted by functional inactivation of CX3CR1. Notably, we found a strong association between the CX3CR1Surf+ status and a metabolic shift away from the OXPHOS pathway and towards glycolysis. Based on these findings, we conducted further studies by assessing the short- and long-term effects of CX3CR1 activation on the metabolic profile of prostate cancer cells. Furthermore, in vivo studies with tumor-bearing mice treated with FX-68 revealed the effects of this compound on the metabolic profiles of cancer cells harvested from tumors in the skeleton and soft tissues. Our work reports for the first time the association of CX3CR1 with the metabolic status of prostate cancer cells. We also provide evidence that interfering with CX3CR1 signaling could impede a metabolic switch promoted by target organs and sustaining metastatic progression.
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Details
- Title
- Abstract 2567: CX3CR1 surface expression on metastatic prostate cancer cells is increased by the target organs and is associated with a distinct metabolic phenotype
- Creators
- Ruxu Zhai - Drexel UniversityJieyi Zhang - Drexel UniversityOlimpia Meucci - Drexel UniversityAlessandro Fatatis - Drexel University
- Publication Details
- Cancer research (Chicago, Ill.), v 85(8_Supplement_1), 2567
- Publisher
- American Association of Cancer Research
- Number of pages
- 2
- Resource Type
- Abstract
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:001499827504450
- Other Identifier
- 991022049012104721
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- Web of Science research areas
- Oncology