Variable Response to Chemotherapeutics by a Subpopulation of MCF-7 Breast Cancer Cells

Several different morphologies can be observed in a population of MCF-7 breast cancer cells, but the typical epithelial morphology vastly predominates. After treatment with the chemotherapeutic doxorubicin, the proportion of abnormal morphologies greatly increases. Over the course of recovery from this drug treatment, the population returns back to high proportions of the normal morphologies. However, previous studies in the Brock lab have shown that in rare instances after recovery from doxorubicin treatment, a phenotype termed the "spiky cells" became stable at higher proportions. This population of spiky cells appeared to have characteristics associated with drug-resistant and metastatic cell populations. In this thesis, I tested the aggressive tumor characteristics of this stable spiky subpopulation and whether it responds differently to doxorubicin. I hypothesized that the growth rate, invasiveness, and drug sensitivity of this population would more closely resemble aggressive tumor cells compared with the naïve MCF-7 population. First, I repeated the induction of the spiky subpopulation with a larger sample size, to determine how frequently this spiky subpopulation occurred. Second, I characterized this subpopulation by comparing four groups: untreated controls of both the normal MCF-7 population and the stable spiky population as well as groups from both populations treated with the same concentration of doxorubicin. I performed these comparisons over the 8-week course of recovery from the treatment. These tests included proliferation rate calculations, invasion assays, staining for a critical protein component of cell-cell junctions, and drug sensitivity tests. We found that the spiky subpopulation appeared more aggressive and resistant, with higher invasion and proliferation, fewer surface markers related to cell connections, and decreased drug sensitivity.