Abstract
CX3CR1 surface expression and phenotypic plasticity in metastasis-initiating cells
Cancer research (Chicago, Ill.), v 83(7 Supplement), 1292
04 Apr 2023
Abstract
Metastasis-initiating cells (MICs) display stem cell-like features and cause metastatic recurrences leading to patients' demise. We found that prostate and breast cancer cells with high surface expression of the chemokine receptor CX3CR1 (CX3CR1high) account for ~5-7% of the whole population and are endowed with metastasis-initiating ability and exhibits stemness features, including expression of pluripotency genes Nanog and Oct4a. Notably, impairing CX3CR1 signaling hinders metastatic initiation and progression in mouse models of human disease. We also found that cancer cells lacking surface CX3CR1 expression (CX3CR1low) can re-acquire CX3CR1-associated features over time by undergoing phenotypic plasticity. Accordingly, when grafted as pure CX3CR1low populations these cells could generate disseminated tumors in mice, implying that MICs can emerge from cancer cells lacking stemness features. In vitro studies by flow cytometry show that cell surface re-exposure of CX3CR1 by CX3CR1low cells begins within 2 days post-sorting, with the whole population reaching phenotypic equilibrium at 12-16 days post-sorting. Further mechanistic studies revealed that both CX3CR1 protein trafficking and transcriptional regulation play a role in phenotypic plasticity. Additionally, disseminated tumors in mice harbor higher percentages of CX3CR1high cells than in vitro cultures, suggesting that the tissue microenvironment of target organs promotes phenotypic plasticity. These findings nominate CX3CR1 as a novel marker of MICs and provide conceptual ground for future development of approaches targeting CX3CR1 signaling and (re)expression as therapeutic means to prevent or contain metastasis initiation and progression.
Metrics
32 Record Views
Details
- Title
- CX3CR1 surface expression and phenotypic plasticity in metastasis-initiating cells
- Creators
- Jieyi Zhang - Drexel UniversityYetunde Oyende - Drexel UniversityJennifer Lynch - Drexel UniversityOlimpia Meucci - Drexel UniversityAlessandro Fatatis - Drexel University
- Publication Details
- Cancer research (Chicago, Ill.), v 83(7 Supplement), 1292
- Conference
- American Association for Cancer Research Annual Meeting 2023 (Orlando, Florida, United States, 14 Apr 2023–19 Apr 2023)
- Publisher
- American Association for Cancer Research (AACR)
- Number of pages
- 1
- Resource Type
- Abstract
- Language
- English
- Academic Unit
- College of Medicine; Pharmacology and Physiology
- Web of Science ID
- WOS:001008193602225
- Other Identifier
- 991020524237004721
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Oncology