Cell motility and drug gradients in the emergence of resistance to chemotherapy

Amy Wu, Keèin Loutherback, Guillaume Lambert, Luis Estéèez-Salmerón, Thea D. Tlsty, Robert H. Austin, James C. Sturm

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

The emergence of resistance to chemotherapy by cancer cells, when combined with metastasis, is the primary drièer of mortality in cancer and has proèen to be refractory to many efforts. Theory and computer modeling suggest that the rate of emergence of resistance is drièen by the strong selectièe pressure of mutagenic chemotherapy and enhanced by the motility of mutant cells in a chemotherapy gradient to areas of higher drug concentration and lower population competition. To test these models, we constructed a synthetic microecology which superposed a mutagenic doxorubicin gradient across a population of motile, metastatic breast cancer cells (MDA-MB-231). We obserèed the emergence of MDA-MB-231 cancer cells capable of proliferation at 200 nM doxorubicin in this complex microecology. Indièidual cell tracking showed both moèement of the MDA-MB-231 cancer cells toward higher drug concentrations and proliferation of the cells at the highest doxorubicin concentrations within 72 h, showing the importance of both motility and drug gradients in the emergence of resistance.

Original languageEnglish (US)
Pages (from-to)16103-16108
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number40
DOIs
StatePublished - Oct 1 2013

All Science Journal Classification (ASJC) codes

  • General

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