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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Impeding Circulating Tumor Cell Reseeding Decelerates Metastatic Progression and Potentiates Chemotherapy
Molecular cancer research, v 16(12), pp 1844-1854
01 Dec 2018
PMID: 30115759
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Circulating tumor cells (CTCs) are commonly detected in the systemic blood of patients with cancer with metastatic tumors. However, the mechanisms controlling the viability of cancer cells in blood and length of time spent in circulation, as well as their potential for generating additional tumors are still undefined. Here, it is demonstrated that CX3CR1, a chemokine receptor, drives reseeding of breast CTCs to multiple organs. Antagonizing this receptor dramatically impairs the progression of breast cancer cells in a relevant model of human metastatic disease, by affecting both tumor growth and numerical expansion. Notably, therapeutic targeting of CX3CR1 prolongs CTC permanence in the blood, both promoting their spontaneous demise by apoptosis and counteracting metastatic reseeding. These effects lead to containment of metastatic progression and extended survival. Finally, targeting CX3CR1 improves blood exposure of CTCs to doxorubicin and in combination with docetaxel shows synergistic effects in containing overall tumor burden.
Implications: The current findings shed light on CTCs reseeding dynamics and support the development of CX3CR1 antagonism as a viable strategy to counteract metastatic progression. (C) 2018 AACR.
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Details
- Title
- Impeding Circulating Tumor Cell Reseeding Decelerates Metastatic Progression and Potentiates Chemotherapy
- Creators
- Chen Qian - Drexel UniversityAsurayya Worrede-Mahdi - Drexel UniversityFei Shen - JanssenAnthony DiNatale - Drexel UniversityRamanpreet Kaur - Drexel UniversityQiang Zhang - Feinberg Sch Med, Lurie Comprehens Canc Ctr, Dept Med Hematol & Oncol, Chicago, IL USAMassimo Cristofanilli - Department of Medicine-Hematology and Oncology, Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Chicago, Illinois.Olimpia Meucci - Drexel UniversityAlessandro Fatatis - Drexel University
- Publication Details
- Molecular cancer research, v 16(12), pp 1844-1854
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 11
- Grant note
- BC150659 / Department of Defense, Breast Cancer Program Breakthrough Award Level 2; United States Department of Defense Wallace H. Coulter Foundation CA202929 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01CA202929 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) Breast Cancer Alliance
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000452375800004
- Scopus ID
- 2-s2.0-85057763922
- Other Identifier
- 991019167822704721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Cell Biology
- Oncology