Impeding Circulating Tumor Cell Reseeding Decelerates Metastatic Progression and Potentiates Chemotherapy
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 01, 2018
- Source ID
- 10.1158/1541-7786.mcr-18-0302
Entities
People
- Alessandro Fatatis
- Anthony Dinatale
- Asurayya Worrede-mahdi
- Chen Qian
- Fei Shen
- Massimo Cristofanilli
- Olimpia Meucci
- Qiang Zhang
- Ramanpreet Kaur
Organizations
- Breast Cancer Alliance
- Congressionally Directed Medical Research Programs
- Drexel University
- Feinberg School of Medicine
- Janssen Pharmaceutica
- National Cancer Institute
- Thomas Jefferson University
- Wallace H. Coulter Foundation