Women with germline BRCA1 mutations (BRCA1) have increased risk for hereditary breast cancer. Cancer initiation in BRCA1 is associated with premalignant changes in breast epithelium; however, the role of the epithelium-associated stromal niche during BRCA1-driven tumor initiation remains unclear. Here we show that the premalignant stromal niche promotes epithelial proliferation and mutant BRCA1-driven tumorigenesis in trans. Using single-cell RNA sequencing analysis of human preneoplastic BRCA1 and noncarrier breast tissues, we show distinct changes in epithelial homeostasis including increased proliferation and expansion of basal-luminal intermediate progenitor cells. Additionally, BRCA1 stromal cells show increased expression of pro-proliferative paracrine signals. In particular, we identify pre-cancer-associated fibroblasts (pre-CAFs) that produce protumorigenic factors including matrix metalloproteinase 3 (MMP3), which promotes BRCA1-driven tumorigenesis in vivo. Together, our findings demonstrate that precancerous stroma in BRCA1 may elevate breast cancer risk through the promotion of epithelial proliferation and an accumulation of luminal progenitor cells with altered differentiation.
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http://dx.doi.org/10.1038/s41588-023-01298-x | DOI Listing |
Methods Mol Biol
December 2024
Department of Experimental Medicine, Biotechnology, and Molecular Biology Section, Luigi Vanvitelli Campania University, Naples, Italy.
Mesenchymal stromal cells (MSCs) are a heterogeneous population of non-hematopoietic adult stem cells derived from the embryonic mesoderm. They possess self-renewal and multipotent differentiation capabilities, allowing them to give rise to mesodermal cell types, such as osteoblasts, chondroblasts, and adipocytes, as well as non-mesodermal cells, including neuron-like cells and endothelial cells. MSCs play a vital role in maintaining homeostasis across various tissues by facilitating tissue repair, immune regulation, and inflammatory response balance.
View Article and Find Full Text PDFHistochem Cell Biol
December 2024
Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Hematopoietic stem cells (HSCs) reside in a milieu that supports their functions, differentiation, and survival. This niche consists of several types of cells, including mesenchymal stem/stromal cells, endothelial cells, osteoblasts, megakaryocytes, macrophages, adipocytes, lymphoid cells, and nerve fibers. The interactions between these cells and HSCs have a role in HSC fate.
View Article and Find Full Text PDFRegen Med
December 2024
Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Aims: This phase I trial assessed the safety and potential efficacy of monthly 3 dose intravenous infusion of allogeneic bone marrow-derived clonal mesenchymal stromal cells (BM-cMSCs) in refractory rheumatoid arthritis (RA) patients over 24 weeks.
Patients & Methods: Six patients with refractory RA received BM-cMSC infusions at one-month intervals over a 24-week period. Safety outcomes included adverse events (AEs) and serious adverse events (SAEs).
ACS Omega
December 2024
Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön katu 34, Tampere FI-33520, Finland.
While bioactive glasses (BaGs) have been studied mainly for bone applications, studies have also shown their potential for soft tissue engineering. Incorporating therapeutic ions, such as lithium (Li), strontium (Sr), and boron (B) into the BaGs, has been found to promote angiogenesis and wound healing. However, a systematic study on the impact of Li, Sr, B, and the other ions in the BaGs, has not been conducted on a wide range of cells.
View Article and Find Full Text PDFBackground: Loss of stromal interaction molecule 1 (STIM1) expression in smooth muscle cells protects against ischemia-reperfusion (I/R) injury. Whether and how decreased STIM1 expression in cardiomyocytes (CM) impacts cardiac remodeling in response to I/R injury remains unknown.
Objective: To examine mechanisms by which decreased CM-STIM1 expression in the adult heart modulates cardiac function before and after I/R injury.
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