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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Subsets of cancer cells expressing CX3CR1 are endowed with metastasis-initiating properties and resistance to chemotherapy
Oncogene, v 41(9), pp 1337-1351
Feb 2022
PMID: 34999735
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Metastasis-initiating cells (MICs) display stem cell-like features, cause metastatic recurrences and defy chemotherapy, which leads to patients' demise. Here we show that prostate and breast cancer patients harbor contingents of tumor cells with high expression of CX3CR1, OCT4a (POU5F1), and NANOG. Impairing CX3CR1 expression or signaling hampered the formation of tumor spheroids by cell lines from which we isolated small subsets co-expressing CX3CR1 and stemness-related markers, similarly to patients' tumors. These rare CX3CR1
cells show transcriptomic profiles enriched in pathways that regulate pluripotency and endowed with metastasis-initiating behavior in murine models. Cancer cells lacking these features (CX3CR1
) were capable of re-acquiring CX3CR1-associated features over time, implying that MICs can continuously emerge from non-stem cancer cells. CX3CR1 expression also conferred resistance to docetaxel, and prolonged treatment with docetaxel selected CX3CR1
phenotypes with de-enriched transcriptomic profiles for apoptotic pathways. These findings nominate CX3CR1 as a novel marker of stem-like tumor cells and provide conceptual ground for future development of approaches targeting CX3CR1 signaling and (re)expression as therapeutic means to prevent or contain metastasis initiation.
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Details
- Title
- Subsets of cancer cells expressing CX3CR1 are endowed with metastasis-initiating properties and resistance to chemotherapy
- Creators
- Anthony DiNatale - Drexel UniversityRamanpreet Kaur - Drexel UniversityChen Qian - Cedars-Sinai Medical CenterJieyi Zhang - Drexel UniversityMichael Marchioli - Drexel UniversityDarin Ipe - Drexel UniversityMaria Castelli - Drexel UniversityChris M McNair - Kimmel Cancer CenterGaurav Kumar - Kimmel Cancer CenterOlimpia Meucci - Drexel UniversityAlessandro Fatatis - Drexel University
- Publication Details
- Oncogene, v 41(9), pp 1337-1351
- Publisher
- Springer Nature
- Grant note
- R01 CA202929 / NCI NIH HHS P30 CA056036 / NCI NIH HHS R37 DA015014 / NIDA NIH HHS 5P30CA056036-21 / U.S. Department of Health & Human Services | NIH | Office of Extramural Research, National Institutes of Health (OER)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000740423700003
- Scopus ID
- 2-s2.0-85122700213
- Other Identifier
- 991019167850904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- Genetics & Heredity
- Oncology