期刊
CANCERS
卷 13, 期 19, 页码 -出版社
MDPI
DOI: 10.3390/cancers13194885
关键词
circulating tumor cells (CTCs); metastatic breast cancer (mBC); lineage negative/lineage-positive(Lin-/Lin plus ) cell populations; CTC plasticity; epithelial cell adhesion molecule/cytokeratins (EpCAM/CKs); RareCyte; single-cell transcriptomics; 10x Genomics Chromium
类别
资金
- NIH [1R01 CA193213]
- Project Translational Award from UNM Comprehensive Cancer Center
- NIH CTCS Award
- UNM Comprehensive Cancer Center Support grant [NCI P30CA118100]
- State of New Mexico
- NCI [P30CA046934]
CTCs, defined as nucleated cells positive for specific markers, can initiate fatal metastasis in breast cancer patients. Challenges in understanding CTC heterogeneity and metastatic propensities remain, but studying the gene interactions associated with CTCs could lead to novel therapeutic interventions.
Fatal metastasis occurs when circulating tumor cells (CTCs) disperse through the blood to initiate a new tumor at specific sites distant from the primary tumor. CTCs have been classically defined as nucleated cells positive for epithelial cell adhesion molecule and select cytokeratins (EpCAM/CK/DAPI), while negative for the common lymphocyte marker CD45. The enumeration of CTCs allows an estimation of the overall metastatic burden in breast cancer patients, but challenges regarding CTC heterogeneity and metastatic propensities persist, and their decryption could improve therapies. CTCs from metastatic breast cancer (mBC) patients were captured using the RareCyte(TM) Cytefinder II platform. The Lin- and Lin+ (CD45+) cell populations isolated from the blood of three of these mBC patients were analyzed by single-cell transcriptomic methods, which identified a variety of immune cell populations and a cluster of cells with a distinct gene expression signature, which includes both cells expressing EpCAM/CK (classic CTCs) and cells possessing an array of genes not previously associated with CTCs. This study put forward notions that the identification of these genes and their interactions will promote novel areas of analysis by dissecting properties underlying CTC survival, proliferation, and interaction with circulatory immune cells. It improves upon capabilities to measure and interfere with CTCs for impactful therapeutic interventions.
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