Abstract ED02-02: Notch defines the tumor initiating cell in non-small cell lung cancer

Zheng, Yanyan; Cruz, Cecile de la; Sayles, Leanne C.; Alleyn-Chin, Chris; Knaak, Tim D.; Bigos, Marty; Xu, Yue; Hoang, Chuong D; Shrager, Joseph; Sweet-Cordero, E. Alejandro; Jackson, Erica L.

doi:10.1158/1940-6207.PREV-12-ED02-02

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Animal Models of Carcinogenesis and Chemoprevention| January 23 2014

Abstract ED02-02: Notch defines the tumor initiating cell in non-small cell lung cancer

Yanyan Zheng;

Yanyan Zheng

1Cancer Biology Program, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, 2Genentech, Inc., South San Francisco, CA, 3Stanford Shared FACS Facility, Center for Molecular and Genetic Medicine, Stanford University, Stanford, CA, 4Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, 5Department of Biology, San Francisco State University, San Francisco CA. 6These authors contributed equally to this work. *equal contribution

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Cecile de la Cruz;

Cecile de la Cruz

1Cancer Biology Program, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, 2Genentech, Inc., South San Francisco, CA, 3Stanford Shared FACS Facility, Center for Molecular and Genetic Medicine, Stanford University, Stanford, CA, 4Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, 5Department of Biology, San Francisco State University, San Francisco CA. 6These authors contributed equally to this work. *equal contribution

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Leanne C. Sayles;

Leanne C. Sayles

1Cancer Biology Program, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, 2Genentech, Inc., South San Francisco, CA, 3Stanford Shared FACS Facility, Center for Molecular and Genetic Medicine, Stanford University, Stanford, CA, 4Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, 5Department of Biology, San Francisco State University, San Francisco CA. 6These authors contributed equally to this work. *equal contribution

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Chris Alleyn-Chin;

Chris Alleyn-Chin

1Cancer Biology Program, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, 2Genentech, Inc., South San Francisco, CA, 3Stanford Shared FACS Facility, Center for Molecular and Genetic Medicine, Stanford University, Stanford, CA, 4Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, 5Department of Biology, San Francisco State University, San Francisco CA. 6These authors contributed equally to this work. *equal contribution

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Tim D. Knaak;

Tim D. Knaak

1Cancer Biology Program, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, 2Genentech, Inc., South San Francisco, CA, 3Stanford Shared FACS Facility, Center for Molecular and Genetic Medicine, Stanford University, Stanford, CA, 4Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, 5Department of Biology, San Francisco State University, San Francisco CA. 6These authors contributed equally to this work. *equal contribution

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Marty Bigos;

Marty Bigos

1Cancer Biology Program, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, 2Genentech, Inc., South San Francisco, CA, 3Stanford Shared FACS Facility, Center for Molecular and Genetic Medicine, Stanford University, Stanford, CA, 4Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, 5Department of Biology, San Francisco State University, San Francisco CA. 6These authors contributed equally to this work. *equal contribution

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Yue Xu;

Yue Xu

1Cancer Biology Program, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, 2Genentech, Inc., South San Francisco, CA, 3Stanford Shared FACS Facility, Center for Molecular and Genetic Medicine, Stanford University, Stanford, CA, 4Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, 5Department of Biology, San Francisco State University, San Francisco CA. 6These authors contributed equally to this work. *equal contribution

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Chuong D Hoang;

Chuong D Hoang

1Cancer Biology Program, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, 2Genentech, Inc., South San Francisco, CA, 3Stanford Shared FACS Facility, Center for Molecular and Genetic Medicine, Stanford University, Stanford, CA, 4Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, 5Department of Biology, San Francisco State University, San Francisco CA. 6These authors contributed equally to this work. *equal contribution

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Joseph Shrager;

Joseph Shrager

1Cancer Biology Program, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, 2Genentech, Inc., South San Francisco, CA, 3Stanford Shared FACS Facility, Center for Molecular and Genetic Medicine, Stanford University, Stanford, CA, 4Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, 5Department of Biology, San Francisco State University, San Francisco CA. 6These authors contributed equally to this work. *equal contribution

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E. Alejandro Sweet-Cordero;

E. Alejandro Sweet-Cordero

1Cancer Biology Program, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, 2Genentech, Inc., South San Francisco, CA, 3Stanford Shared FACS Facility, Center for Molecular and Genetic Medicine, Stanford University, Stanford, CA, 4Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, 5Department of Biology, San Francisco State University, San Francisco CA. 6These authors contributed equally to this work. *equal contribution

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Erica L. Jackson

1Cancer Biology Program, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, 2Genentech, Inc., South San Francisco, CA, 3Stanford Shared FACS Facility, Center for Molecular and Genetic Medicine, Stanford University, Stanford, CA, 4Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, 5Department of Biology, San Francisco State University, San Francisco CA. 6These authors contributed equally to this work. *equal contribution

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Author & Article Information

Online ISSN: 1940-6215

Print ISSN: 1940-6207

2012

Cancer Prev Res (Phila) (2012) 5 (11_Supplement): ED02-02.

https://doi.org/10.1158/1940-6207.PREV-12-ED02-02

Abstract

We investigated heterogeneity of tumorigenic capacity in KrasG12D and KrasG12D; Trp53 fl/fl mouse models of non-small cell lung cancer. Loss of Trp53 greatly enhances self-renewal in vitro and tumor propagating capacity in vivo. A conserved set of markers including CD24, ITGB4 and Notch enriches for a rare population of tumor initiating cells (TICs) in tumors driven by oncogenic Kras regardless of disease stage, or the presence or absence of Trp53. Notch marks TICs and Notch signaling is also required for their self-renewal and tumor propagating capacity. Using primary human NSCLC ex vivo cultures, we demonstrate a role for Notch signaling in the self-renewal of human tumor cells. Using multiple methods of Notch3 specific inhibition we demonstrate a Trp53-independent role for Notch3 in the maintenance of TICs in mouse lung tumor models.

Citation Format: Yanyan Zheng, Cecile de la Cruz, Leanne C. Sayles, Chris Alleyn-Chin, Tim D. Knaak, Marty Bigos, Yue Xu, Chuong D Hoang, Joseph Shrager, E. Alejandro Sweet-Cordero, Erica L. Jackson,. Notch defines the tumor initiating cell in non-small cell lung cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr ED02-02.

2012

Abstract ED02-02: Notch defines the tumor initiating cell in non-small cell lung cancer

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