Samineni Sridhar, Glackin Carlotta, Shively John E
Irell & Manella City of Hope Graduate School of Biological Sciences, Duarte, CA 91010, USA.
Int J Breast Cancer. 2011;2011:381080. doi: 10.4061/2011/381080. Epub 2010 Nov 7.
Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) is a morphogen in an in vitro model for lumen formation and plays a similar role in breast epithelial cells implanted in humanized mammary fat pads in NOD-SCID mice. Although extra cellular matrix alone is sufficient to stimulate lumen formation in CEACAM1 transfected MCF-7 cells grown in 3D culture, there is an additional requirement for stromal or mesenchymal cells (MSCs) for these cells to form xenografts with glandular structures in an orthotopic site. We demonstrate that optimal in vitro conditions include both Matrigel and MSCs and that the inclusion of collagen I inhibits xenograft differentiation. Additionally, there is no need to remove the nascent murine mammary gland. The previously observed difference in gland development between the long and short cytoplasmic domain isoforms of CEACAM1 is no longer observed in pregnant NOD/SCID mice suggesting that stimulation of the mammary fat pad by pregnancy critically affects xenograft differentiation.
癌胚抗原相关细胞黏附分子-1（CEACAM1）在体外管腔形成模型中是一种形态发生素，并且在植入NOD-SCID小鼠人源化乳腺脂肪垫的乳腺上皮细胞中发挥类似作用。尽管单独的细胞外基质足以刺激在三维培养中生长的CEACAM1转染的MCF-7细胞形成管腔，但这些细胞要在原位形成具有腺结构的异种移植物，还额外需要基质细胞或间充质细胞（MSC）。我们证明，最佳体外条件包括基质胶和MSC，并且包含I型胶原会抑制异种移植物分化。此外，无需去除新生小鼠乳腺。先前观察到的CEACAM1长细胞质结构域和短细胞质结构域异构体之间在腺体发育上的差异，在怀孕的NOD/SCID小鼠中不再出现，这表明怀孕对乳腺脂肪垫的刺激严重影响异种移植物分化。
