Abstract B48: Intratumor ploidy heterogeneity as a chemoresistance mechanism in triple-negative breastcancer

In this study, we isolated and functionally characterized the diploid and polyploid sub-populations derived from TNBC cell lines. DNA ploidy was assessed in Hoechst 33342 stained cells using flow cytometry. Cells with greater than 4N DNA content were considered as polyploid. Next, we analyzed cell proliferation in HCC1937 cells using CFSE and DNA labeling. Live-cell imaging was performed on flow-sorted diploid and polyploid cells using IncuCyte Zoom to monitor cell proliferation in the absence and presence of mitotic inhibitor (docetaxel).Results: DNA ploidy analysis identified presence of polyploid cells in HCC1395 and HCC1937 cell lines at a frequency of 6.7% and 5.8% respectively. Polyploid cells have higher forward-scatter than diploid cells suggesting that they are larger in size. In addition, nuclear staining with Hoechst 33342 showed that giant polyploid cells contain enlarged and/or multiple nuclei. Time-lapse microscopy in polyploid cells revealed mitotic structures suggestive of multipolar cell division. Carboxyfluorescein diacetate, succinimidyl ester (CFSE) labeling showed that polyploid cycle slower than the predominant diploid population. Further, the IncuCyte cell proliferation assay also confirmed that sorted polyploid cells divide slower than the diploid cells and displayed resistance to docetaxel.Concusions: These findings indicate that there are functional differences between diploid and polyploid sub-populations. In our future studies, we will examine the ...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Tumor Heterogeneity (Intratumor and Intertumoral): Poster Presentations - Proffered Abstracts Source Type: research