Data from A Human Breast Cell Model of Preinvasive to Invasive Transition

作者：Aylin Rizki, Valerie Marie Weaver, Sun‐Young Lee, Gabriela I. Rozenberg, Koei Chin, Connie A. Myers, Jamie L. Bascom, Joni D. Mott, Jeremy R. Semeiks, Leslie R. Grate, I. Saira Mian, Alexander D. Borowsky, Roy Andrew Jensen, Michael Oladimeji Idowu, Fanqing Chen, David J. Chen, OLE WILLIAM PETERSEN, Joe W. Gray, Mina J. Bissell · 年份：2023 · DOI：10.1158/0008-5472.c.6497556 · 研究领域：Cancer Cells and Metastasis、Biomarkers in Disease Mechanisms、TGF-β signaling in diseases

Abstract A crucial step in human breast cancer progression is the acquisition of invasiveness. There is a distinct lack of human cell culture models to study the transition from preinvasive to invasive phenotype as it may occur “spontaneously” in vivo. To delineate molecular alterations important for this transition, we isolated human breast epithelial cell lines that showed partial loss of tissue polarity in three-dimensional reconstituted basement membrane cultures. These cells remained noninvasive; however, unlike their nonmalignant counterparts, they exhibited a high propensity to acquire invasiveness through basement membrane in culture. The genomic aberrations and gene expression profiles of the cells in this model showed a high degree of similarity to primary breast tumor profiles. The xenograft tumors formed by the cell lines in three different microenvironments in nude mice displayed metaplastic phenotypes, including squamous and basal characteristics, with invasive cells exhibiting features of higher-grade tumors. To find functionally significant changes in transition from preinvasive to invasive phenotype, we performed attribute profile clustering analysis on the list of genes differentially expressed between preinvasive and invasive cells. We found integral membrane proteins, transcription factors, kinases, transport molecules, and chemokines to be highly represented. In addition, expression of matrix metalloproteinases MMP9, MMP13, MMP15, and MMP17 was up-regulat...