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

• DOI: 10.1073/pnas.1314385110
• Publication Date: 2013-09-18T03:28:54Z
• Authors: Amy Wu; Kevin Loutherback; Guillaume Lambert; Luis Estévez-Salm...; Thea D. Tlsty; Robert H. Austin; James C. Sturm
• Keywords: Microecology

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