Analysis of circulating breast cancer cell heterogeneity and interactions with peripheral blood mononuclear cells.
Biomarkers, Tumor
/ metabolism
Breast Neoplasms
/ blood
Epithelial-Mesenchymal Transition
Female
Humans
Leukocytes, Mononuclear
/ pathology
Neoplastic Cells, Circulating
/ pathology
Prognosis
Receptor, ErbB-2
/ metabolism
Receptors, Estrogen
/ metabolism
Receptors, Progesterone
/ metabolism
Tumor Cells, Cultured
breast cancer
circulating tumor cells
metastasis
tumor microenvironment
Journal
Molecular carcinogenesis
ISSN: 1098-2744
Titre abrégé: Mol Carcinog
Pays: United States
ID NLM: 8811105
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
02
04
2020
revised:
17
07
2020
accepted:
20
07
2020
pubmed:
22
8
2020
medline:
3
11
2020
entrez:
22
8
2020
Statut:
ppublish
Résumé
For solid tumors, extravasation of cancer cells and their survival in circulation represents a critical stage of the metastatic process that lacks complete understanding. Gaining insight into interactions between circulating tumor cells (CTCs) and other peripheral blood mononuclear cells (PBMCs) may provide valuable prognostic information. The purpose of this study was to use single-cell RNA-sequencing (scRNA-seq) of liquid biopsies from breast cancer patients to begin defining intravascular interactions. We captured CTCs from the peripheral blood of breast cancer patients using size-exclusion membranes followed by scRNA-seq of enriched CTCs and carry-over PBMCs. Transcriptome analysis identified two populations of CTCs: one enriched for transcripts indicative of estrogen responsiveness and increased proliferation and another enriched for transcripts characteristic of reduced proliferation and epithelial-mesenchymal transition (EMT). We applied interactome and pathway analysis to determine interactions between CTCs and other captured cells. Our analysis predicted for enhanced immune evasion in the CTC population with EMT characteristics. In addition, PD-1/PD-L1 pathway activation and T cell exhaustion were predicted in T cells isolated from breast cancer patients compared with normal T cells. We conclude that scRNA-seq of breast cancer CTCs generally stratifies them into two types based on their proliferative and epithelial state and differential potential to interact with PBMCs. Better understanding of CTC subtypes and their intravascular interactions may help design treatments directed against CTCs with high metastatic and immune-evasive competence.
Identifiants
pubmed: 32822091
doi: 10.1002/mc.23242
pmc: PMC7895311
mid: NIHMS1660865
doi:
Substances chimiques
Biomarkers, Tumor
0
Receptors, Estrogen
0
Receptors, Progesterone
0
ERBB2 protein, human
EC 2.7.10.1
Receptor, ErbB-2
EC 2.7.10.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1129-1139Subventions
Organisme : NICHD NIH HHS
ID : K12 HD068372
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA046934
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA205044
Pays : United States
Informations de copyright
© 2020 Wiley Periodicals LLC.
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