Identification and Targeting of Long-Term Tumor-Propagating Cells in Small Cell Lung Cancer

Nadine S. Jahchan; Jing Shan Lim; Becky Bola; Karen Morris; Garrett Seitz; Kim Q. Tran; Lei Xu; Francesca Trapani; Christopher J. Morrow; Sandra Cristea; Garry L. Coles; Dian Yang; Dedeepya Vaka; Michael S. Kareta; Julie George; Pawel K. Mazur; Thuyen Nguyen; Wade C. Anderson; Scott J. Dylla; Fiona Blackhall; Martin Peifer; Caroline Dive; Julien Sage

doi:10.1016/j.celrep.2016.06.021

Identification and Targeting of Long-Term Tumor-Propagating Cells in Small Cell Lung Cancer

Nadine S. Jahchan, Jing Shan Lim, Becky Bola, Karen Morris, Garrett Seitz, Kim Q. Tran, Lei Xu, Francesca Trapani, Christopher J. Morrow, Sandra Cristea, Garry L. Coles, Dian Yang, Dedeepya Vaka, Michael S. Kareta, Julie George, Pawel K. Mazur, Thuyen Nguyen, Wade C. Anderson, Scott J. Dylla, Fiona BlackhallMartin Peifer, Caroline Dive, Julien Sage

Research output: Contribution to journal › Article › peer-review

65 Scopus citations

Abstract

Small cell lung cancer (SCLC) is a neuroendocrine lung cancer characterized by fast growth, early dissemination, and rapid resistance to chemotherapy. We identified a population of long-term tumor-propagating cells (TPCs) in a mouse model of SCLC. This population, marked by high levels of EpCAM and CD24, is also prevalent in human primary SCLC tumors. Murine SCLC TPCs are numerous and highly proliferative but not intrinsically chemoresistant, indicating that not all clinical features of SCLC are linked to TPCs. SCLC TPCs possess a distinct transcriptional profile compared to non-TPCs, including elevated MYC activity. Genetic and pharmacological inhibition of MYC in SCLC cells to non-TPC levels inhibits long-term propagation but not short-term growth. These studies identify a highly tumorigenic population of SCLC cells in mouse models, cell lines, and patient tumors and a means to target them in this most fatal form of lung cancer.

Original language	English (US)
Pages (from-to)	644-656
Number of pages	13
Journal	Cell Reports
Volume	16
Issue number	3
DOIs	https://doi.org/10.1016/j.celrep.2016.06.021
State	Published - Jul 19 2016
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2016.06.021

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Jahchan, N. S., Lim, J. S., Bola, B., Morris, K., Seitz, G., Tran, K. Q., Xu, L., Trapani, F., Morrow, C. J., Cristea, S., Coles, G. L., Yang, D., Vaka, D., Kareta, M. S., George, J., Mazur, P. K., Nguyen, T., Anderson, W. C., Dylla, S. J., ... Sage, J. (2016). Identification and Targeting of Long-Term Tumor-Propagating Cells in Small Cell Lung Cancer. Cell Reports, 16(3), 644-656. https://doi.org/10.1016/j.celrep.2016.06.021

Jahchan, NS, Lim, JS, Bola, B, Morris, K, Seitz, G, Tran, KQ, Xu, L, Trapani, F, Morrow, CJ, Cristea, S, Coles, GL, Yang, D, Vaka, D, Kareta, MS, George, J, Mazur, PK, Nguyen, T, Anderson, WC, Dylla, SJ, Blackhall, F, Peifer, M, Dive, C & Sage, J 2016, 'Identification and Targeting of Long-Term Tumor-Propagating Cells in Small Cell Lung Cancer', Cell Reports, vol. 16, no. 3, pp. 644-656. https://doi.org/10.1016/j.celrep.2016.06.021

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title = "Identification and Targeting of Long-Term Tumor-Propagating Cells in Small Cell Lung Cancer",

abstract = "Small cell lung cancer (SCLC) is a neuroendocrine lung cancer characterized by fast growth, early dissemination, and rapid resistance to chemotherapy. We identified a population of long-term tumor-propagating cells (TPCs) in a mouse model of SCLC. This population, marked by high levels of EpCAM and CD24, is also prevalent in human primary SCLC tumors. Murine SCLC TPCs are numerous and highly proliferative but not intrinsically chemoresistant, indicating that not all clinical features of SCLC are linked to TPCs. SCLC TPCs possess a distinct transcriptional profile compared to non-TPCs, including elevated MYC activity. Genetic and pharmacological inhibition of MYC in SCLC cells to non-TPC levels inhibits long-term propagation but not short-term growth. These studies identify a highly tumorigenic population of SCLC cells in mouse models, cell lines, and patient tumors and a means to target them in this most fatal form of lung cancer.",

author = "Jahchan, {Nadine S.} and Lim, {Jing Shan} and Becky Bola and Karen Morris and Garrett Seitz and Tran, {Kim Q.} and Lei Xu and Francesca Trapani and Morrow, {Christopher J.} and Sandra Cristea and Coles, {Garry L.} and Dian Yang and Dedeepya Vaka and Kareta, {Michael S.} and Julie George and Mazur, {Pawel K.} and Thuyen Nguyen and Anderson, {Wade C.} and Dylla, {Scott J.} and Fiona Blackhall and Martin Peifer and Caroline Dive and Julien Sage",

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AU - Bola, Becky

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AU - Seitz, Garrett

AU - Tran, Kim Q.

AU - Xu, Lei

AU - Trapani, Francesca

AU - Morrow, Christopher J.

AU - Cristea, Sandra

AU - Coles, Garry L.

AU - Yang, Dian

AU - Vaka, Dedeepya

AU - Kareta, Michael S.

AU - George, Julie

AU - Mazur, Pawel K.

AU - Nguyen, Thuyen

AU - Anderson, Wade C.

AU - Dylla, Scott J.

AU - Blackhall, Fiona

AU - Peifer, Martin

AU - Dive, Caroline

AU - Sage, Julien

PY - 2016/7/19

Y1 - 2016/7/19

N2 - Small cell lung cancer (SCLC) is a neuroendocrine lung cancer characterized by fast growth, early dissemination, and rapid resistance to chemotherapy. We identified a population of long-term tumor-propagating cells (TPCs) in a mouse model of SCLC. This population, marked by high levels of EpCAM and CD24, is also prevalent in human primary SCLC tumors. Murine SCLC TPCs are numerous and highly proliferative but not intrinsically chemoresistant, indicating that not all clinical features of SCLC are linked to TPCs. SCLC TPCs possess a distinct transcriptional profile compared to non-TPCs, including elevated MYC activity. Genetic and pharmacological inhibition of MYC in SCLC cells to non-TPC levels inhibits long-term propagation but not short-term growth. These studies identify a highly tumorigenic population of SCLC cells in mouse models, cell lines, and patient tumors and a means to target them in this most fatal form of lung cancer.

AB - Small cell lung cancer (SCLC) is a neuroendocrine lung cancer characterized by fast growth, early dissemination, and rapid resistance to chemotherapy. We identified a population of long-term tumor-propagating cells (TPCs) in a mouse model of SCLC. This population, marked by high levels of EpCAM and CD24, is also prevalent in human primary SCLC tumors. Murine SCLC TPCs are numerous and highly proliferative but not intrinsically chemoresistant, indicating that not all clinical features of SCLC are linked to TPCs. SCLC TPCs possess a distinct transcriptional profile compared to non-TPCs, including elevated MYC activity. Genetic and pharmacological inhibition of MYC in SCLC cells to non-TPC levels inhibits long-term propagation but not short-term growth. These studies identify a highly tumorigenic population of SCLC cells in mouse models, cell lines, and patient tumors and a means to target them in this most fatal form of lung cancer.

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Identification and Targeting of Long-Term Tumor-Propagating Cells in Small Cell Lung Cancer

Abstract

ASJC Scopus subject areas

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