Tumorigenesis, Phenotypic Reversion, and Dormancy

Apicobasal polarity, properly positioned cell-cell contacts, and attachment to basement membrane are fundamental characteristics of simple glandular epithelia, such as the mammary gland. The development and maintenance of this polarized structure is essential for the formation of tissue architecture, control of proliferation, and the differentiated function of epithelial cells. Loss of architectural intactness and polarity is one of the pathological hallmarks of epithelial carcinoma.

Our laboratory has developed an assay in which primary or phenotypically normal human breast epithelial cells cultured in a laminin-rich basement membrane (BM) undergo a three-dimensional (3D) reorganization to form structures which mimic in vivo acinar structures in culture. In contrast, cells from tumors or cancer cell lines continue to proliferate into apolar, amorphous structures, providing a versatile method to distinguish the response of normal and cancer cells to their microenvironment. We have shown that the tumorigenic mammary epithelial cells (HMT-3522) can be reverted into organized and correctly polarized structures when the activity of either epidermal growth factor receptor (EGFR) or b1 integrin, which are overexpressed and overactivated, is reduced and only when these cells are grown in a 3D BM context.

 Pathways of The Minimum Integration Unit

Recent Publications

Bissell MJ, Rizki A, Mian IS.Tissue architecture: the ultimate regulator of breast epithelial function. Curr Opin Cell Biol. 2003 Dec; 15(6): 753-62.

Kenny PA, Bissell MJ. Tumor reversion: correction of malignant behavior by microenvironmental cues. Int J Cancer. 2003 Dec 10; 107(5): 688-95.

Schmeichel KL, Bissell MJRelated Articles, Links Modeling tissue-specific signaling and organ function in three dimensions. J Cell Sci. 2003 Jun 15; 116(Pt 12): 2377-88.

Wang F, Hansen RK, Radisky D, Yoneda T, Barcellos-Hoff MH, Petersen OW, Turley EA, Bissell MJ. Phenotypic reversion or death of cancer cells by altering signaling pathways in three-dimensional contexts. JNatl Cancer Inst. 2002 Oct 2; 94(19): 1494-503