The isolation and characterization of CTC subsets related to breast cancer dormancy

Monika Vishnoi; Sirisha Peddibhotla; Wei Yin; Antonio T. Scamardo; Goldy C. George; David S. Hong; Dario Marchetti

doi:10.1038/srep17533

The isolation and characterization of CTC subsets related to breast cancer dormancy

Monika Vishnoi, Sirisha Peddibhotla, Wei Yin, Antonio T. Scamardo, Goldy C. George, David S. Hong, Dario Marchetti

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96 Scopus citations

Abstract

Uncovering CTCs phenotypes offer the promise to dissect their heterogeneity related to metastatic competence. CTC survival rates are highly variable and this can lead to many questions as yet unexplored properties of CTCs responsible for invasion and metastasis vs dormancy. We isolated CTC subsets from peripheral blood of patients diagnosed with or without breast cancer brain metastasis. CTC subsets were selected for EpCAM negativity but positivity for CD44⁺/CD24^- stem cell signature; along with combinatorial expression of uPAR and int β1, two markers directly implicated in breast cancer dormancy mechanisms. CTC subsets were cultured in vitro generating 3D CTC tumorspheres which were interrogated for biomarker profiling and biological characteristics. We identified proliferative and invasive properties of 3D CTC tumorspheres distinctive upon uPAR/int β1 combinatorial expression. The molecular characterization of uPAR/int β1 CTC subsets may enhance abilities to prospectively identify patients who may be at high risk of developing BCBM.

Original language	English (US)
Article number	17533
Journal	Scientific reports
Volume	5
DOIs	https://doi.org/10.1038/srep17533
State	Published - Dec 1 2015

ASJC Scopus subject areas

General

MD Anderson CCSG core facilities

Flow Cytometry and Cellular Imaging Facility

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10.1038/srep17533

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title = "The isolation and characterization of CTC subsets related to breast cancer dormancy",

abstract = "Uncovering CTCs phenotypes offer the promise to dissect their heterogeneity related to metastatic competence. CTC survival rates are highly variable and this can lead to many questions as yet unexplored properties of CTCs responsible for invasion and metastasis vs dormancy. We isolated CTC subsets from peripheral blood of patients diagnosed with or without breast cancer brain metastasis. CTC subsets were selected for EpCAM negativity but positivity for CD44+/CD24- stem cell signature; along with combinatorial expression of uPAR and int β1, two markers directly implicated in breast cancer dormancy mechanisms. CTC subsets were cultured in vitro generating 3D CTC tumorspheres which were interrogated for biomarker profiling and biological characteristics. We identified proliferative and invasive properties of 3D CTC tumorspheres distinctive upon uPAR/int β1 combinatorial expression. The molecular characterization of uPAR/int β1 CTC subsets may enhance abilities to prospectively identify patients who may be at high risk of developing BCBM.",

author = "Monika Vishnoi and Sirisha Peddibhotla and Wei Yin and Scamardo, {Antonio T.} and George, {Goldy C.} and Hong, {David S.} and Dario Marchetti",

note = "Funding Information: This study was supported by NIH grant (1R01 CA160335), the Breast Cancer Breakthrough Award from the Department of Defense-Congressional Directed Medical Research Programs (W81XWH-14-1-0214), CPRIT grant (RP140181) and by a grant from the Avon Foundation for Women to D.M. Support for STR DNA fingerprinting core was provided by the Cancer Center Support Grant-funded Characterized Cell Line Core (NCI CA016672). We are thankful to Dr. Joan Massague, Memorial Sloan Kettering Cancer Center, NY, USA for providing us two brain metastatic cell lines: MDA-MB231Br and CN34Br. We are also thankful to Ms. Wendy Schober for flow cytometry analysis at Flow Cytometry and Cellular Imaging core facility at MD Anderson, Houston, TX, and to Drs. Debalina Goswami-Sewell and Debasish Boral for editing figures.",

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AU - George, Goldy C.

AU - Hong, David S.

AU - Marchetti, Dario

N1 - Funding Information: This study was supported by NIH grant (1R01 CA160335), the Breast Cancer Breakthrough Award from the Department of Defense-Congressional Directed Medical Research Programs (W81XWH-14-1-0214), CPRIT grant (RP140181) and by a grant from the Avon Foundation for Women to D.M. Support for STR DNA fingerprinting core was provided by the Cancer Center Support Grant-funded Characterized Cell Line Core (NCI CA016672). We are thankful to Dr. Joan Massague, Memorial Sloan Kettering Cancer Center, NY, USA for providing us two brain metastatic cell lines: MDA-MB231Br and CN34Br. We are also thankful to Ms. Wendy Schober for flow cytometry analysis at Flow Cytometry and Cellular Imaging core facility at MD Anderson, Houston, TX, and to Drs. Debalina Goswami-Sewell and Debasish Boral for editing figures.

PY - 2015/12/1

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N2 - Uncovering CTCs phenotypes offer the promise to dissect their heterogeneity related to metastatic competence. CTC survival rates are highly variable and this can lead to many questions as yet unexplored properties of CTCs responsible for invasion and metastasis vs dormancy. We isolated CTC subsets from peripheral blood of patients diagnosed with or without breast cancer brain metastasis. CTC subsets were selected for EpCAM negativity but positivity for CD44+/CD24- stem cell signature; along with combinatorial expression of uPAR and int β1, two markers directly implicated in breast cancer dormancy mechanisms. CTC subsets were cultured in vitro generating 3D CTC tumorspheres which were interrogated for biomarker profiling and biological characteristics. We identified proliferative and invasive properties of 3D CTC tumorspheres distinctive upon uPAR/int β1 combinatorial expression. The molecular characterization of uPAR/int β1 CTC subsets may enhance abilities to prospectively identify patients who may be at high risk of developing BCBM.

AB - Uncovering CTCs phenotypes offer the promise to dissect their heterogeneity related to metastatic competence. CTC survival rates are highly variable and this can lead to many questions as yet unexplored properties of CTCs responsible for invasion and metastasis vs dormancy. We isolated CTC subsets from peripheral blood of patients diagnosed with or without breast cancer brain metastasis. CTC subsets were selected for EpCAM negativity but positivity for CD44+/CD24- stem cell signature; along with combinatorial expression of uPAR and int β1, two markers directly implicated in breast cancer dormancy mechanisms. CTC subsets were cultured in vitro generating 3D CTC tumorspheres which were interrogated for biomarker profiling and biological characteristics. We identified proliferative and invasive properties of 3D CTC tumorspheres distinctive upon uPAR/int β1 combinatorial expression. The molecular characterization of uPAR/int β1 CTC subsets may enhance abilities to prospectively identify patients who may be at high risk of developing BCBM.

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The isolation and characterization of CTC subsets related to breast cancer dormancy

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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