Abstract 5191: Targeting CX3CR1 Impairs the reseeding and colonization of circulating tumor cells and decelerates metastatic progression
| Autor: | Alessandro Fatatis, Asurayya Worrede-Mahdi, Chen Qian, Joseph M. Salvino, Fei Shen, Olimpia Meucci, Ramanpreet Kaur |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research business.industry Cancer medicine.disease 03 medical and health sciences Chemokine receptor 030104 developmental biology 0302 clinical medicine Circulating tumor cell Oncology Docetaxel Tumor progression 030220 oncology & carcinogenesis Cancer cell CX3CR1 Cancer research Medicine Doxorubicin business medicine.drug |
| Zdroj: | Cancer Research. 78:5191-5191 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2018-5191 |
| Popis: | This study aims to understand the mechanisms and dynamics by which cancer cells, departing from existing metastases as circulating cancer cells (CTCs), further seed and colonize skeleton and soft tissues, expanding metastatic spreading and 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 FX-68, a novel small-molecule antagonist for this receptor, effectively contains both number of lesions and total tumor burden in animal models of metastatic disease. Here we established that FX-68 impairs the reseeding of skeleton and soft tissue and that the CTCs unable to reseed and forced to remain in the blood eventually succumb to apoptotic death. The metastatic potential of CTCs was confirmed by reinoculation experiments as well as by forcefully mobilizing cancer cells from metastases back in the blood and assessing the number of additional lesions generated, in the presence and absence of FX-68. Furthermore, we found that prolonging the permanence of CTCs in the blood by targeting CX3CR1 with FX-68 improved exposure of cancer cells to the chemotherapy drugs doxorubicin or docetaxel significantly decreased tumor progression and extended overall survival. Finally, we found evidence that cancer cells seeding the skeleton despite the inhibition of CX3CR1 failed to develop into tumors, suggesting a role of CX3CR1 expression in the metastasis-initiating properties of breast cancer cells. In summary, our results strongly support developing CX3CR1 antagonists and promoting their clinical use, as this approach will provide novel and effective tools to contain the progression of metastatic disease in patients. Citation Format: Chen Qian, Asurayya Worrede-Mahdi, Ramanpreet Kaur, Fei Shen, Joseph Salvino, Olimpia Meucci, Alessandro Fatatis. Targeting CX3CR1 Impairs the reseeding and colonization of circulating tumor cells and decelerates metastatic progression [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 5191. |
| Databáze: | OpenAIRE |
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