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Abstract 5799: Targeting CX3CR1 impairs the reseeding of cancer cells recirculating from metastatic tumors
Journal article   Open access   Peer reviewed

Abstract 5799: Targeting CX3CR1 impairs the reseeding of cancer cells recirculating from metastatic tumors

Chen Qian, Asurayya Worrede-Mahdi, Ramanpreet Kaur, Fei Shen, Joseph Salvino, Olimpia Meucci and Alessandro Fatatis
Cancer research (Chicago, Ill.), v 77(13_Supplement), pp 5799-5799
01 Jul 2017
DOI: https://doi.org/10.1158/1538-7445.AM2017-5799
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https://doi.org/10.1158/1538-7445.am2017-5799View
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Abstract

Abstract Cancer cells re-enter systemic blood from established metastatic tumors. Recent evidence indicates that these recirculating cancer cells further seed and colonize skeleton and soft tissues to expand metastatic dissemination, thus precipitating the clinical progression to terminal disease. We have previously shown that the chemokine receptor CX3CR1 is implicated in the metastatic seeding of breast cancer cells and that novel small-molecule antagonists for this receptor effectively contains the number and size of secondary tumors in animal models. Using the same models, we now report that targeting CX3CR1 also restrains the re-seeding of skeleton and soft-tissue by circulating cancer cells (CTCs) departing from existing metastatic lesions. Notably, we also found that CTCs unable to re-seed are forced to remain in the blood circulation longer, eventually succumbing to apoptotic death. It has been proposed that when either spontaneously or forcibly (re)circulating in the blood, cancer cells from solid tumors are more vulnerable to the effects of both cytotoxic and targeted therapeutics. Given the role of CX3CR1 antagonists in prolonging the time spent by CTCs in the blood, we sought to assess whether these compounds could synergize with docetaxel by extending bioavailability and its cytotoxic effects. Thus, we tested this paradigm on CTCs departing from skeletal and soft-tissue lesions generated by breast and prostate cancer cells in mice. Based on the results obtained from these experiments, it can be concluded that implementing the development of CX3CR1 antagonists and promoting their clinical use will provide novel and effective tools to contain the progression of metastatic disease in cancer patients. Citation Format: Chen Qian, Asurayya Worrede-Mahdi, Ramanpreet Kaur, Fei Shen, Joseph Salvino, Olimpia Meucci, Alessandro Fatatis. Targeting CX3CR1 impairs the reseeding of cancer cells recirculating from metastatic tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5799. doi:10.1158/1538-7445.AM2017-5799

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Oncology
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