Dataset Information

BMI-1 Targeting Interferes with Patient-Derived Tumor-Initiating Cell Survival and Tumor Growth in Prostate Cancer.

ABSTRACT: Current prostate cancer management calls for identifying novel and more effective therapies. Self-renewing tumor-initiating cells (TICs) hold intrinsic therapy resistance and account for tumor relapse and progression. As BMI-1 regulates stem cell self-renewal, impairing BMI-1 function for TIC-tailored therapies appears to be a promising approach.We have previously developed a combined immunophenotypic and time-of-adherence assay to identify CD49bhiCD29hiCD44hi cells as human prostate TICs. We utilized this assay with patient-derived prostate cancer cells and xenograft models to characterize the effects of pharmacologic inhibitors of BMI-1.We demonstrate that in cell lines and patient-derived TICs, BMI-1 expression is upregulated and associated with stem cell-like traits. From a screened library, we identified a number of post-transcriptional small molecules that target BMI-1 in prostate TICs. Pharmacologic inhibition of BMI-1 in patient-derived cells significantly decreased colony formation in vitro and attenuated tumor initiation in vivo, thereby functionally diminishing the frequency of TICs, particularly in cells resistant to proliferation- and androgen receptor-directed therapies, without toxic effects on normal tissues.Our data offer a paradigm for targeting TICs and support the development of BMI-1-targeting therapy for a more effective prostate cancer treatment. Clin Cancer Res; 22(24); 6176-91. ©2016 AACR.

SUBMITTER: Bansal N

PROVIDER: S-EPMC5159329 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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BMI-1 Targeting Interferes with Patient-Derived Tumor-Initiating Cell Survival and Tumor Growth in Prostate Cancer.

Bansal Nitu N Bartucci Monica M Yusuff Shamila S Davis Stephani S Flaherty Kathleen K Huselid Eric E Patrizii Michele M Jones Daniel D Cao Liangxian L Sydorenko Nadiya N Moon Young-Choon YC Zhong Hua H Medina Daniel J DJ Kerrigan John J Stein Mark N MN Kim Isaac Y IY Davis Thomas W TW DiPaola Robert S RS Bertino Joseph R JR Sabaawy Hatem E HE

Clinical cancer research : an official journal of the American Association for Cancer Research 20160615 24

<h4>Purpose</h4>Current prostate cancer management calls for identifying novel and more effective therapies. Self-renewing tumor-initiating cells (TICs) hold intrinsic therapy resistance and account for tumor relapse and progression. As BMI-1 regulates stem cell self-renewal, impairing BMI-1 function for TIC-tailored therapies appears to be a promising approach.<h4>Experimental design</h4>We have previously developed a combined immunophenotypic and time-of-adherence assay to identify CD49b<sup>h ...[more]

PMID: 27307599

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Dataset Information

BMI-1 Targeting Interferes with Patient-Derived Tumor-Initiating Cell Survival and Tumor Growth in Prostate Cancer.

Publications

BMI-1 Targeting Interferes with Patient-Derived Tumor-Initiating Cell Survival and Tumor Growth in Prostate Cancer.

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