Impeding circulating tumor cell reseeding decelerates metastatic progression and potentiates chemotherapy

Chen Qian, Asurayya Worrede-Mahdi, Fei Shen, Anthony DiNatale, Ramanpreet Kaur, Qiang Zhang, Massimo Cristofanilli, Olimpia Meucci, Alessandro Fatatis*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1844-1854
Number of pages11
JournalMolecular Cancer Research
Volume16
Issue number12
DOIs
StatePublished - Dec 1 2018

Fingerprint

Circulating Neoplastic Cells
Drug Therapy
docetaxel
Neoplasms
Breast Neoplasms
Chemokine Receptors
Tumor Burden
Doxorubicin
Blood Cells
Cell Survival
Apoptosis
Survival
Growth

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

Cite this

Qian, Chen ; Worrede-Mahdi, Asurayya ; Shen, Fei ; DiNatale, Anthony ; Kaur, Ramanpreet ; Zhang, Qiang ; Cristofanilli, Massimo ; Meucci, Olimpia ; Fatatis, Alessandro. / Impeding circulating tumor cell reseeding decelerates metastatic progression and potentiates chemotherapy. In: Molecular Cancer Research. 2018 ; Vol. 16, No. 12. pp. 1844-1854.
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Impeding circulating tumor cell reseeding decelerates metastatic progression and potentiates chemotherapy. / Qian, Chen; Worrede-Mahdi, Asurayya; Shen, Fei; DiNatale, Anthony; Kaur, Ramanpreet; Zhang, Qiang; Cristofanilli, Massimo; Meucci, Olimpia; Fatatis, Alessandro.

In: Molecular Cancer Research, Vol. 16, No. 12, 01.12.2018, p. 1844-1854.

Research output: Contribution to journalArticle

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AU - Qian, Chen

AU - Worrede-Mahdi, Asurayya

AU - Shen, Fei

AU - DiNatale, Anthony

AU - Kaur, Ramanpreet

AU - Zhang, Qiang

AU - Cristofanilli, Massimo

AU - Meucci, Olimpia

AU - Fatatis, Alessandro

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