A human breast cell model of preinvasive to invasive transition

Aylin Rizki, Valerie M. Weaver, Sun Young Lee, Gabriela I. Rozenberg, Kwang-Yung Chin, Connie A. Myers, Jamie L. Bascom, Joni D. Mott, Jeremy R. Semeiks, Leslie R. Grate, I. Saira Mian, Alexander D. Borowsky, Roy A. Jensen, Michael O. Idowu, Fanqing Chen, David J. Chen, Ole W. Petersen, Joe Gray, Mina J. Bissell

Research output: Contribution to journalArticle

104 Citations (Scopus)

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-regulated in the invasive cells. Using small interfering RNA-based approaches, we found these MMPs to be required for the invasive phenotype. This model provides a new tool for dissection of mechanisms by which preinvasive breast cells could acquire invasiveness in a metaplastic context.

Original languageEnglish (US)
Pages (from-to)1378-1387
Number of pages10
JournalCancer Research
Volume68
Issue number5
DOIs
StatePublished - Mar 1 2008
Externally publishedYes

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Breast
Phenotype
Matrix Metalloproteinases
Basement Membrane
Breast Neoplasms
Tumor Cell Line
Transcriptome
Chemokines
Heterografts
Nude Mice
Small Interfering RNA
Cluster Analysis
Dissection
Membrane Proteins
Transcription Factors
Phosphotransferases
Cell Culture Techniques
Epithelial Cells
Cell Line
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Rizki, A., Weaver, V. M., Lee, S. Y., Rozenberg, G. I., Chin, K-Y., Myers, C. A., ... Bissell, M. J. (2008). A human breast cell model of preinvasive to invasive transition. Cancer Research, 68(5), 1378-1387. https://doi.org/10.1158/0008-5472.CAN-07-2225

A human breast cell model of preinvasive to invasive transition. / Rizki, Aylin; Weaver, Valerie M.; Lee, Sun Young; Rozenberg, Gabriela I.; Chin, Kwang-Yung; Myers, Connie A.; Bascom, Jamie L.; Mott, Joni D.; Semeiks, Jeremy R.; Grate, Leslie R.; Mian, I. Saira; Borowsky, Alexander D.; Jensen, Roy A.; Idowu, Michael O.; Chen, Fanqing; Chen, David J.; Petersen, Ole W.; Gray, Joe; Bissell, Mina J.

In: Cancer Research, Vol. 68, No. 5, 01.03.2008, p. 1378-1387.

Research output: Contribution to journalArticle

Rizki, A, Weaver, VM, Lee, SY, Rozenberg, GI, Chin, K-Y, Myers, CA, Bascom, JL, Mott, JD, Semeiks, JR, Grate, LR, Mian, IS, Borowsky, AD, Jensen, RA, Idowu, MO, Chen, F, Chen, DJ, Petersen, OW, Gray, J & Bissell, MJ 2008, 'A human breast cell model of preinvasive to invasive transition', Cancer Research, vol. 68, no. 5, pp. 1378-1387. https://doi.org/10.1158/0008-5472.CAN-07-2225
Rizki A, Weaver VM, Lee SY, Rozenberg GI, Chin K-Y, Myers CA et al. A human breast cell model of preinvasive to invasive transition. Cancer Research. 2008 Mar 1;68(5):1378-1387. https://doi.org/10.1158/0008-5472.CAN-07-2225
Rizki, Aylin ; Weaver, Valerie M. ; Lee, Sun Young ; Rozenberg, Gabriela I. ; Chin, Kwang-Yung ; Myers, Connie A. ; Bascom, Jamie L. ; Mott, Joni D. ; Semeiks, Jeremy R. ; Grate, Leslie R. ; Mian, I. Saira ; Borowsky, Alexander D. ; Jensen, Roy A. ; Idowu, Michael O. ; Chen, Fanqing ; Chen, David J. ; Petersen, Ole W. ; Gray, Joe ; Bissell, Mina J. / A human breast cell model of preinvasive to invasive transition. In: Cancer Research. 2008 ; Vol. 68, No. 5. pp. 1378-1387.
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