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Deletion of Integrin‐associated CD151 Impairs Branching Morphogenesis and Activity of Progenitor Cells in the Mammary Gland
Author(s) -
Yang Xiuwei,
Baldwin Lauren
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.890.15
Subject(s) - progenitor cell , laminin , microbiology and biotechnology , biology , morphogenesis , integrin , myoepithelial cell , angiogenesis , extracellular matrix , progenitor , transcription factor , stem cell , cell , immunology , cancer research , genetics , immunohistochemistry , gene
Tetraspanin CD151 interacts with laminin‐binding integrins (i.e., a3b1, a6b1 and a6b4) and other cell surface molecules to control diverse biological processes. Here we reported a novel role of CD151 in the branching morphogenesis and progenitor cells during the pubertal development of mammary glands. In contrast to the disruption of laminin‐binding integrins, CD151 removal in mice enhanced the tertiary branching of mammary glands by 2.4 fold and the number of terminal end buds (TEBs) by 30%, while having a minimum influence on main ducts or secondary branching. Consistent with these changes are the skewed distribution of basal/myoepithelial cells and a 3.2‐fold increase in proliferating Ki‐67‐positive cells. These observations suggest that CD151 may impact the branching morphogenesis of mammary glands by upregulating the activities of bipotent luminal progenitor cells. Indeed, our analyses indicate that upon CD151 removal the proportion of CD24 Hi CD49f Low luminal progenitor cells increased by 34%, and their proliferating and differentiating activities were upregulated. Importantly, fibronectin, a pro‐branching extracellular matrix (ECM) protein deposited underlying mammary epithelial or progenitor cells, increased by > 7.2 fold. Moreover, there was a concomitant increase in the expression and nuclear distribution of Slug, a transcription factor being previously implicated in the maintenance of mammary progenitor cell activities. Taken together, our studies demonstrate that integrin‐associated CD151 regulates mammary branching morphogenesis by maintaining progenitor cell activities, ECM integrity and transcription program.