title: CD151 represses mammary gland development by maintaining the niches of progenitor cells.
abstract: Tetraspanin CD151 interacts with laminin-binding integrins (i.e., α3β1, α6β1 and α6β4) and other cell surface molecules to control diverse cellular and physiological processes, ranging from cell adhesion, migration and survival to tissue architecture and homeostasis. Here, we report a novel role of CD151 in maintaining the branching morphogenesis and activity of 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 in mammary glands by 2.4-fold and the number of terminal end buds (TEBs) by 30%, while having minimal influence on either primary or secondary ductal branching. Consistent with these morphological changes are the skewed distribution of basal/myoepithelial cells and a 3.2-fold increase in proliferating Ki67-positive cells. These novel observations suggest that CD151 impacts the branching morphogenesis of mammary glands by upregulating the activities of bipotent progenitor cells. Indeed, our subsequent analyses indicate that upon CD151 removal the proportion of CD24(Hi)CD49f(Low) progenitor cells in the mammary gland increased by 34%, and their proliferating and differentiating activities were significantly 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 implicated in the maintenance of mammary progenitor cell activities. Taken together, our studies demonstrate that integrin-associated CD151 represses mammary branching morphogenesis by controlling progenitor cell activities, ECM integrity and transcription program.
authors.affiliation: a Cancer Institute; First Affiliated Hospital ; China Medical University ; Shenyang , China.
authors.forename: Yuanqin
authors.initials: Y
authors.lastname: Yin
authors.forename: Xinyu
authors.initials: X
authors.lastname: Deng
authors.forename: Zeyi
authors.initials: Z
authors.lastname: Liu
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Baldwin
authors.forename: Jason
authors.initials: J
authors.lastname: Lefringhouse
authors.forename: Jiayang
authors.initials: J
authors.lastname: Zhang
authors.forename: John T
authors.initials: JT
authors.lastname: Hoff
authors.forename: Sonia F
authors.initials: SF
authors.lastname: Erfani
authors.forename: Edmund B
authors.initials: EB
authors.lastname: Rucker
authors.forename: Kathleen
authors.initials: K
authors.lastname: O'Connor
authors.forename: Chunming
authors.initials: C
authors.lastname: Liu
authors.forename: Yadi
authors.initials: Y
authors.lastname: Wu
authors.forename: Binhua P
authors.initials: BP
authors.lastname: Zhou
authors.forename: Xiuwei H
authors.initials: XH
authors.lastname: Yang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism*; D051379:Mice; D009024:Morphogenesis; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D055153:Stem Cell Niche; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D060185:Tetraspanin 24 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C554716:Cd151 protein, mouse; D016023:Integrins; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D060185:Tetraspanin 24; D014157:Transcription Factors; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases
keywords: CD151 tetraspanin; ECM, extracellular matrix; EMT, epithelial-mesenchymal transition; LB, laminin-binding; Slug; TEB, terminal end bud; extracellular matrix; integrin; mammary gland