Abstract
One cancer cell line is believed to be composed of numerous clones with different drug sensitivity. We sought to investigate the difference of drug-response pattern in clones from a cell line or from a single cell. We showed that 22 clones derived from 4T1 cells were drastically different from each other with respect to drug-response pattern against 11 anticancer drugs and expression profile of 19 genes associated with drug resistance or sensitivity. Similar results were obtained using daughter clones derived from a single 4T1 cell. Each daughter clone showed distinct drug-response pattern and gene expression profile. Similar results were also obtained using Bcap37 cells. We conclude that a single cancer cell can rapidly produce a population of cells with high heterogeneity of drug response and the acquisition of drug-response heterogeneity is random.
Highlights
Cancer drug resistance is a major obstacle for chemotherapy
We showed that 22 clones derived from 4T1 cells were drastically different from each other with respect to drug-response pattern against 11 anticancer drugs and expression profile of 19 genes associated with drug resistance or sensitivity
The main purpose of this study is to investigate how big the difference of daughter clones from a single cell origin can be
Summary
Cancer drug resistance is a major obstacle for chemotherapy. Drug resistance can be arisen from heterogeneity of cancer cells, which exhibit differences on the aspects of growth, apoptosis, morphology, genetic instability [3, 4]. The major factors determining cancer cell heterogeneity are genetic makeup and epigenetic expression, origin of cancer stem cells, and tumor microenvironment, etc [5,6,7,8,9,10]. The advance of the technology to sequence the whole genome of a single cell has further unraveled the heterogenic nature of cancer cells [11, 12]. The intratumoral heterogeneity confounds significantly cancer therapy and is a challenge for precision medicine [13]
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