Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models

Huiping Liu, Manishkumar R. Patel, Jennifer A. Prescher, Antonia Patsialou, Dalong Qian, Jiahui Lin, Susanna Wen, Ya Fang Chang, Michael H. Bachmann, Yohei Shimono, Piero Dalerba, Maddalena Adorno, Neethan Lobo, Janet Bueno, Frederick M. Dirbas, Sumanta Goswami, George Somlo, John S. Condeelis, Christopher H. Contag, Sanjiv Sam GambhirMichael F. Clarke

Research output: Contribution to journalArticle

266 Citations (Scopus)

Abstract

To examine the role of breast cancer stem cells (BCSCs) in metastasis, we generated human-in-mouse breast cancer orthotopic models using patient tumor specimens, labeled with optical reporter fusion genes. These models recapitulate human cancer features not captured with previous models, including spontaneous metastasis in particular, and provide a useful platform for studies of breast tumor initiation and progression. With noninvasive imaging approaches, as few as 10 cells of stably labeled BCSCs could be tracked in vivo, enabling studies of early tumor growth and spontaneous metastasis. These advances in BCSC imaging revealed that CD44+ cells from both primary tumors and lung metastases are highly enriched for tumor-initiating cells. Our metastatic cancer models, combined with noninvasive imaging techniques, constitute an integrated approach that could be applied to dissect the molecular mechanisms underlying the dissemination of metastatic CSCs (MCSCs) and to explore therapeutic strategies targeting MCSCs in general or to evaluate individual patient tumor cells and predict response to therapy.

Original languageEnglish (US)
Pages (from-to)18115-18120
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number42
DOIs
StatePublished - Oct 19 2010

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Neoplastic Stem Cells
Breast Neoplasms
Neoplasm Metastasis
Neoplasms
Reporter Genes
Lung
Therapeutics
Growth

Keywords

  • Bioluminescence imaging
  • Breast cancer
  • Fused optical reporters
  • Human-in-mouse cancer models

ASJC Scopus subject areas

  • General

Cite this

Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models. / Liu, Huiping; Patel, Manishkumar R.; Prescher, Jennifer A.; Patsialou, Antonia; Qian, Dalong; Lin, Jiahui; Wen, Susanna; Chang, Ya Fang; Bachmann, Michael H.; Shimono, Yohei; Dalerba, Piero; Adorno, Maddalena; Lobo, Neethan; Bueno, Janet; Dirbas, Frederick M.; Goswami, Sumanta; Somlo, George; Condeelis, John S.; Contag, Christopher H.; Gambhir, Sanjiv Sam; Clarke, Michael F.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 42, 19.10.2010, p. 18115-18120.

Research output: Contribution to journalArticle

Liu, H, Patel, MR, Prescher, JA, Patsialou, A, Qian, D, Lin, J, Wen, S, Chang, YF, Bachmann, MH, Shimono, Y, Dalerba, P, Adorno, M, Lobo, N, Bueno, J, Dirbas, FM, Goswami, S, Somlo, G, Condeelis, JS, Contag, CH, Gambhir, SS & Clarke, MF 2010, 'Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models', Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 42, pp. 18115-18120. https://doi.org/10.1073/pnas.1006732107
Liu, Huiping ; Patel, Manishkumar R. ; Prescher, Jennifer A. ; Patsialou, Antonia ; Qian, Dalong ; Lin, Jiahui ; Wen, Susanna ; Chang, Ya Fang ; Bachmann, Michael H. ; Shimono, Yohei ; Dalerba, Piero ; Adorno, Maddalena ; Lobo, Neethan ; Bueno, Janet ; Dirbas, Frederick M. ; Goswami, Sumanta ; Somlo, George ; Condeelis, John S. ; Contag, Christopher H. ; Gambhir, Sanjiv Sam ; Clarke, Michael F. / Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 42. pp. 18115-18120.
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abstract = "To examine the role of breast cancer stem cells (BCSCs) in metastasis, we generated human-in-mouse breast cancer orthotopic models using patient tumor specimens, labeled with optical reporter fusion genes. These models recapitulate human cancer features not captured with previous models, including spontaneous metastasis in particular, and provide a useful platform for studies of breast tumor initiation and progression. With noninvasive imaging approaches, as few as 10 cells of stably labeled BCSCs could be tracked in vivo, enabling studies of early tumor growth and spontaneous metastasis. These advances in BCSC imaging revealed that CD44+ cells from both primary tumors and lung metastases are highly enriched for tumor-initiating cells. Our metastatic cancer models, combined with noninvasive imaging techniques, constitute an integrated approach that could be applied to dissect the molecular mechanisms underlying the dissemination of metastatic CSCs (MCSCs) and to explore therapeutic strategies targeting MCSCs in general or to evaluate individual patient tumor cells and predict response to therapy.",
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