Identification of molecularly unique tumor-associated mesenchymal stromal cells in breast cancer patients.
Jonathan A R GordonMark F EvansPrachi N GhuleKyra LeePamela VacekBrian L SpragueDonald L WeaverGary S SteinJanet L SteinPublished in: PloS one (2023)
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.
Keyphrases
- gene expression
- mesenchymal stem cells
- extracellular matrix
- single cell
- umbilical cord
- bone marrow
- dna methylation
- cell proliferation
- breast cancer cells
- cell therapy
- induced apoptosis
- rna seq
- genome wide
- poor prognosis
- papillary thyroid
- signaling pathway
- free survival
- bioinformatics analysis
- cell cycle arrest
- case report
- stem cells
- cell cycle
- squamous cell
- high throughput
- cell death
- transcription factor
- binding protein
- escherichia coli
- genome wide identification
- candida albicans