TY - JOUR
T1 - CD151 represses mammary gland development by maintaining the niches of progenitor cells
AU - Yin, Yuanqin
AU - Deng, Xinyu
AU - Liu, Zeyi
AU - Baldwin, Lauren A.
AU - Lefringhouse, Jason
AU - Zhang, Jiayang
AU - Hoff, John T.
AU - Erfani, Sonia F.
AU - Rucker, Edmund B.
AU - O'Connor, Kathleen
AU - Liu, Chunming
AU - Wu, Yadi
AU - Zhou, Binhua P.
AU - Yang, Xiuwei H.
N1 - Publisher Copyright:
© 2014 Taylor &Francis Group, LLC.
PY - 2014/9/1
Y1 - 2014/9/1
N2 - Tetraspanin CD151 interacts with laminin-binding integrins (i.e., a3b1, a6b1 and a6b4) 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 CD24HiCD49fLow 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.
AB - Tetraspanin CD151 interacts with laminin-binding integrins (i.e., a3b1, a6b1 and a6b4) 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 CD24HiCD49fLow 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.
KW - CD151 tetraspanin
KW - Extracellular matrix
KW - Integrin
KW - Mammary gland
KW - Slug
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UR - http://www.scopus.com/inward/citedby.url?scp=84907450670&partnerID=8YFLogxK
U2 - 10.4161/15384101.2015.945823
DO - 10.4161/15384101.2015.945823
M3 - Article
C2 - 25486358
AN - SCOPUS:84907450670
SN - 1538-4101
VL - 13
SP - 2707
EP - 2722
JO - Cell Cycle
JF - Cell Cycle
IS - 17
ER -