Effects of Different Tissue Microenvironments on Gene Expression in Breast Cancer Cells

In metastasis, circulating tumor cells penetrate the walls of blood vessels and enter the metastatic target tissue, thereby becoming exposed to novel and relatively unsupportive microenvironments. In the new microenvironments, the tumor cells often remain in a dormant state indefinitely and must adapt before they are able to successfully colonize the tissue. Very little is known about this adaptive process. We studied temporal changes in gene expression when breast cancer cells adapt to survive and grow on brain, bone marrow, and lung tissue maintained in an in vivo culture system, as models of the metastatic colonization of these tissues. We observed the transient activation of genes typically associated with homeostasis and stress during the initial stages of adaptation, followed by the activation of genes that mediate more advanced functions, such as elaboration of cell morphology and cell division, as the cells adapted to thrive in the host tissue microenvironment. We also observed the temporary induction of genes characteristic of the host tissue, which was particularly evident when tumor cells were grown on brain tissue. These early transient gene expression events suggest potential points of therapeutic intervention that are not evident in data from well-established tumors.

Citation: Rondeau G, Abedinpour P, Desai P, Baron VT, Borgstrom P, et al. (2014) Effects of Different Tissue
Microenvironments on Gene Expression in Breast Cancer Cells. PLoS ONE 9(7): e101160.
doi:10.1371/journal.pone.0101160
Editor: Scott A. Weed, West Virginia University, United States of America
Received: March 3, 2014; Accepted: June 2, 2014; Published: July 8, 2014
Copyright: © 2014 Rondeau et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by the California Breast Cancer Research Program (151B-0133), the DOD (W81XWH-09-1-0280), and the NCI (1R21CA133638). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.