Identification of molecularly unique tumor-associated mesenchymal stromal cells in breast cancer patients

The tumor microenvironment is a complex mixture of cell types that bi-directionally interact and influence tumor initiation, progression, recurrence, and patient survival. Mesenchymal stromal cells (MSCs) of the tumor microenvironment engage in crosstalk with cancer cells to mediate epigenetic contr...

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Bibliographic Details
Published in:PloS one 2023-03, Vol.18 (3), p.e0282473-e0282473
Main Authors: Gordon, Jonathan A R, Evans, Mark F, Ghule, Prachi N, Lee, Kyra, Vacek, Pamela, Sprague, Brian L, Weaver, Donald L, Stein, Gary S, Stein, Janet L
Format: Article
Language:English
Subjects:
Analysis
Biology and Life Sciences
Bone marrow
Breast cancer
Breast Neoplasms - diagnosis
Breast Neoplasms - genetics
Cell interactions
Cell Line, Tumor
Cell Proliferation
Cell survival
Colorectal cancer
Crosstalk
Cytokines
Diagnosis
Epigenetic inheritance
Epigenetics
Epithelial-Mesenchymal Transition - genetics
Extracellular matrix
Gastric cancer
Gene expression
Genetic aspects
Growth factors
Health aspects
Humans
Medicine and Health Sciences
Mesenchymal stem cells
Mesenchymal Stem Cells - metabolism
Microscopy
Morphology
Patients
Phenotypes
Prostate cancer
Signal Transduction
Stem cells
Stromal cells
Stromal Cells - metabolism
Transcriptome
Tumor microenvironment
Tumor Microenvironment - genetics
Tumors
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Summary:The tumor microenvironment is a complex mixture of cell types that bi-directionally interact and influence tumor initiation, progression, recurrence, and patient survival. Mesenchymal stromal cells (MSCs) of the tumor microenvironment engage in crosstalk with cancer cells to mediate epigenetic control of gene expression. We identified CD90+ MSCs residing in the tumor microenvironment of patients with invasive breast cancer that exhibit a unique gene expression signature. Single-cell transcriptional analysis of these MSCs in tumor-associated stroma identified a distinct subpopulation characterized by increased expression of genes functionally related to extracellular matrix signaling. Blocking the TGFβ pathway reveals that these cells directly contribute to cancer cell proliferation. Our findings provide novel insight into communication between breast cancer cells and MSCs that are consistent with an epithelial to mesenchymal transition and acquisition of competency for compromised control of proliferation, mobility, motility, and phenotype.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0282473