Reconstruction of functionally normal and malignant human breast tissues in mice
Reconstruction of functionally normal and malignant human breast tissues in mice
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DOI：
10.1073/pnas.0401064101
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发表时间：
2004-04-06
影响因子：
11.1
通讯作者：
Weinberg, RA
中科院分区：
文献类型：
--
作者：
Kuperwasser, C;Chavarria, T;Weinberg, RA
正常乳腺上皮形态发生和体内致癌的研究主要使用啮齿动物模型。研究异种移植人上皮细胞的乳腺形态发生和癌症的努力未能概括人类乳腺发育的全部程度。我们已经开发了一种原位异种移植模型，其中重建乳腺的基质和上皮成分都是人源性的。在植入表面正常的人乳腺上皮细胞之前，对人基质细胞进行遗传修饰，导致良性和恶性病变的生长。该实验模型允许在体内研究人类上皮的形态发生和分化，并强调了异型相互作用在人类乳腺发育和癌变中的关键作用。
The study of normal breast epithelial morphogenesis and carcinogenesis in vivo has largely used rodent models. Efforts at studying mammary morphogenesis and cancer with xenotransplanted human epithelial cells have failed to recapitulate the full extent of development seen in the human breast. We have developed an orthotopic xenograft model in which both the stromal and epithelial components of the reconstructed mammary gland are of human origin. Genetic modification of human stromal cells before the implantation of ostensibly normal human mammary epithelial cells resulted in the outgrowth of benign and malignant lesions. This experimental model allows for studies of human epithelial morphogenesis and differentiation in vivo and underscores the critical role of heterotypic interactions in human breast development and carcinogenesis.