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Evaluation of 6-mercaptopurine in a cell culture model of adaptable triple-negative breast cancer with metastatic potential.

ABSTRACT: Progenitor-like cancer cells that can survive in reversible quiescence when faced with various challenges in the body are often behind disease progression. A lack of glutamine in culture medium, which eliminates >99.9% of proliferating SUM149 triple-negative breast cancer cells, selects such adaptable, pan-resistant cells. Our data support the hypothesis that a lack of glutamine forces the selection of an epigenetic state that does not require a high level of TET2, thus selecting an "undifferentiated" therapy-resistant phenotype as seen in TET2-mutant cancers. Our data suggesting that highly adaptable cells are generated through reprograming of the epigenome and transcriptome led us to evaluate low-dose 6-mercaptopurine as a potential therapy in our model. We found that a long treatment with low-dose 6-mercaptopurine inhibited the proliferation of these adaptable cells to a greater extent than it inhibited parental cells. Importantly, a small percentage of adaptable cells survived a low-dose 6-mercaptopurine treatment in a reversible quiescence, analogous to the persistence of abnormal progenitor-like cells in inflammatory bowel disease, which stays in a durable remission with a 6-mercaptopurine treatment. Based on a biomarkers analysis, a long treatment with 6-mercaptopurine or aspirin partially reversed epithelial to mesenchymal transition in adaptable cancer cells. A cell culture model of adaptable cancer cells that persist in the body will help in discovering superior therapies that can be offered before the disease advances to metastasis.

SUBMITTER: Singh B

PROVIDER: S-EPMC6557209 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Evaluation of 6-mercaptopurine in a cell culture model of adaptable triple-negative breast cancer with metastatic potential.

Singh Balraj B Sarli Vanessa N VN Kinne Hannah E HE Shamsnia Anna A Lucci Anthony A

Oncotarget 20190604 38

Progenitor-like cancer cells that can survive in reversible quiescence when faced with various challenges in the body are often behind disease progression. A lack of glutamine in culture medium, which eliminates >99.9% of proliferating SUM149 triple-negative breast cancer cells, selects such adaptable, pan-resistant cells. Our data support the hypothesis that a lack of glutamine forces the selection of an epigenetic state that does not require a high level of TET2, thus selecting an "undifferent ...[more]

PMID: 31217902

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Dataset Information

Evaluation of 6-mercaptopurine in a cell culture model of adaptable triple-negative breast cancer with metastatic potential.

Publications

Evaluation of 6-mercaptopurine in a cell culture model of adaptable triple-negative breast cancer with metastatic potential.

Similar Datasets

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