EXPRESSION AND FUNCTIONAL-ROLE OF E-CADHERIN AND P-CADHERIN IN MOUSE MAMMARY DUCTAL MORPHOGENESIS AND GROWTH
EXPRESSION AND FUNCTIONAL-ROLE OF E-CADHERIN AND P-CADHERIN IN MOUSE MAMMARY DUCTAL MORPHOGENESIS AND GROWTH
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DOI：
10.1006/dbio.1995.1165
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发表时间：
1995-06-01
影响因子：
2.7
通讯作者：
FRIEDMANN, Y
中科院分区：
文献类型：
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作者：
DANIEL, CW;STRICKLAND, P;FRIEDMANN, Y
乳腺导管及其产生的高度有丝分裂的终芽由两层外胚层来源的上皮组成，形成管中管结构。我们研究了Ca2+依赖性细胞-细胞粘附分子在维持这些层的完整性中的作用。免疫染色显示终芽体细胞和导管管腔细胞外侧膜上有丰富的E-cadherin，但未见P-cadherin。位于基部的帽细胞及其分化后代导管肌上皮细胞仅显示p -钙粘蛋白。我们通过手术植入释放功能阻断抗体的小型缓释塑料植入物来研究这种原位钙粘蛋白表达模式的功能意义。暴露于E-cadherin单克隆抗体的终芽显示体上皮被破坏，上皮细胞在管腔内自由漂浮。上皮DNA合成，通常在这些生长芽中非常高，突然下降。这种生长的减少不是由于细胞损伤，当阻断抗体耗尽时，细胞自发地重新聚集成正常上皮，并恢复DNA合成。P-cadherin单克隆抗体对管腔层无影响，但部分破坏了位于基部的帽细胞层。这些数据表明，E-和p -钙粘蛋白的空间选择性表达是乳腺组织完整性所必需的，这反过来又是正常DNA合成速率的先决条件。(C) 1995学术出版社，Inc。
Mammary ducts, and the highly mitotic terminal end buds from which they are derived, consist of two layers of ectodermally derived epithelium, forming a tube-within-a-tube structure. We investigated the role of Ca2+-dependent cell-cell adhesion molecules in maintaining the integrity of these layers. Immunostaining showed abundant E-cadherin on the lateral membranes of end bud body cells and ductal lumenal cells, but no P-cadherin. The basally located cap cells and their differentiated descendants, the ductal myoepithelial cells, displayed only P-cadherin. We investigated the functional significance of this pattern of cadherin expression in situ by surgically implanting small, slow-release plastic implants releasing function-blocking antibodies. End buds exposed to a monoclonal antibody to E-cadherin showed disruption of the body epithelium, with epithelial cells floating freely in the lumen. Epithelial DNA synthesis, which is normally very high in these growth buds, abruptly declined. That this reduction in growth was not due to cell damage was shown by spontaneous reaggregation of the cells into a normal epithelium, with resumption of DNA synthesis, when the blocking antibody was depleted. A monoclonal antibody to P-cadherin had no effect on the lumenal layer but partially disrupted the basally located cap cell layer. These data indicate that spatially selective expression of E- and P-cadherins is required for mammary tissue integrity, which is in turn a prerequisite for normal rates of DNA synthesis. (C) 1995 Academic Press,Inc.