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Elimination of Human Lung Cancer Stem Cells through Targeting of the Stem Cell Factor–c-kit Autocrine Signaling Loop
Open accessPublished version of a preprint
Abstract
Cancer stem cells (CSC) are thought to be responsible for tumor initiation and tumor regeneration after chemotherapy. Previously, we showed that chemotherapy of non-small cell lung cancer (NSCLC) cells lines can select for outgrowth of highly tumorigenic and metastatic CSCs. The high malignancy of lung CSCs was associated with an efficient cytokine network. In this study, we provide evidence that blocking stem cell factor (SCF)-c-kit signaling is sufficient to inhibit CSC proliferation and survival promoted by chemotherapy. CSCs were isolated from NSCLC cell lines as tumor spheres under CSC-selective conditions and their stem properties were confirmed. In contrast to other tumor cells, CSCs expressed c-kit receptors and produced SCF. Proliferation of CSCs was inhibited by SCF-neutralizing antibodies or by imatinib (Gleevec), an inhibitor of c-kit. Although cisplatin treatment eliminated the majority of tumor cells, it did not eliminate CSCs, whereas imatinib or anti-SCF antibody destroyed CSCs. Significantly, combining cisplatin with imatinib or anti-SCF antibody prevented the growth of both tumor cell subpopulations. Our findings reveal an important role for the SCF-c-kit signaling axis in self-renewal and proliferation of lung CSCs, and they suggest that SCF-c-kit signaling blockade could improve the antitumor efficacy of chemotherapy of human NSCLC.
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“For lung cancer, ALDH, CD44, Oct4, c-kit, and Nestin were shown to be some of the most frequently observed CSCs markers which promote tumor development [53,54,85,86,87].”
From 20-Hydroxyecdysone Confers Antioxidant and Antineoplastic Properties in Human Non-Small Cell Lung Cancer Cells (2023) · cites this paper as [53]
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“Figure 10 demonstrates that 20E treatment at doses of 0.1–100 µM significantly inhibited the expression of all of the CSC markers studied.”
From 20-Hydroxyecdysone Confers Antioxidant and Antineoplastic Properties in Human Non-Small Cell Lung Cancer Cells (2023) · cites this paper as [53]
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Citations
Cites
Prospective identification of tumorigenic breast cancer cells
Al‐Hajj, M., Wicha, M. S., Benito‐Hernández, A., Morrison, S. J., & Clarke, M. F. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0530291100 · Cited by 10,579
Stem cells, cancer, and cancer stem cells
Reya, T., Morrison, S. J., Clarke, M. F., & Weissman, I. L. (2001) · Nature · doi:10.1038/35102167 · Cited by 9,738
Identification of human brain tumour initiating cells
Singh, S. K., Hawkins, C. E., Clarke, I. D., Squire, J. A., Bayani, J., Hide, T., Henkelman, R. M., Cusimano, M. D., & Dirks, P. B. (2004) · Nature · doi:10.1038/nature03128 · Cited by 7,564
The phosphatidylinositol 3-Kinase–AKT pathway in human cancer
Vivanco, I., & Sawyers, C. L. (2002) · Nature reviews. Cancer · doi:10.1038/nrc839 · Cited by 6,155
Druker, B. J., Talpaz, M., Resta, D. J., Peng, B., Buchdunger, E., Ford, J., Lydon, N., Kantarjian, H. M., Capdeville, R., Ohno-Jones, S., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200104053441401 · Cited by 5,237
Identification and expansion of human colon-cancer-initiating cells
Ricci‐Vitiani, L., Lombardi, D. G., Pilozzi, E., Biffoni, M., Todaro, M., Peschle, C., & Maria, R. D. (2006) · Nature · doi:10.1038/nature05384 · Cited by 4,001
Tumour stem cells and drug resistance
Dean, M., Fojo, T., & Bates, S. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1590 · Cited by 3,668
Hermann, P. C., Huber, S. L., Herrler, T., Aicher, A., Ellwart, J. W., Guba, M. O., Bruns, C. J., & Heeschen, C. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.06.002 · Cited by 2,946
In vitro propagation and transcriptional profiling of human mammary stem/progenitor cellsPreprint
Dontu, G., Abdallah, W. M., Foley, J. M., Jackson, K. W., Clarke, M. F., Kawamura, M., & Wicha, M. S. (2003) · Genes & Development · doi:10.1101/gad.1061803 · Cited by 2,413
Kinase Mutations and Imatinib Response in Patients With Metastatic Gastrointestinal Stromal Tumor
Heinrich, M. C., Corless, C. L., Demetri, G. D., Blanke, C. D., von Mehren, M., Joensuu, H., McGreevey, L. S., Chen, C.-J., den Abbeele, A. D. V., Druker, B. J., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.04.190 · Cited by 2,306
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Horstmann, M., Hennenlotter, J., Geiger, L. M., Vogel, U. F., Schmid, H., Kuehs, U., Stenzl, A., & Bedke, J. (2012) · PubMed · Cited by 11
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Skurikhin, Е. G., Pershina, О. V., Zhukova, М. А., Widera, D., Ermakova, N. N., Pan, E. S., Pakhomova, A. V., Morozov, S., Kubatiev, A. A., & Дыгай, А. М. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.778020 · Cited by 11
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Zhou, Y., Wang, L., Sun, Z., Zhang, J., & Wang, X. (2020) · PubMed Central · Cited by 11
Liu, S., Zhang, X., Jiang, Q., & Liang, T. (2020) · FEBS Open Bio · doi:10.1002/2211-5463.12878 · Cited by 10
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Yang, Y., Zhang, W., & Lan, P. (2022) · Cancers · doi:10.3390/cancers14235963 · Cited by 8
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Shi, W. H., Yu, Y. B., Li, Z.-Y., Guo, X.-C., Wei, Z., & Zheng, Z.-H. (2015) · Genetics and Molecular Research · doi:10.4238/2015.november.18.54 · Cited by 3
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Sabisz, M., & Składanowski, A. (2011) · InTech eBooks · doi:10.5772/14359 · Cited by 2
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Deng, J., Lai, G., Zhang, C., Li, K., Zhu, W., Xie, B., & Zhong, X. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e25570 · Cited by 1
Davis, M. L., Gassner, K., Barrueco, R. R., & Llobet‐Navàs, D. (2018) · Springer eBooks · doi:10.1007/978-3-319-90695-9_12 · Cited by 1
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Manjili, R. H. (2011) · Cited by 1
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Abi-Rizk, A. (2017) · International Journal of Molecular Biology Open Access · doi:10.15406/ijmboa.2016.02.00015
Rodrigues, F. S. (2018) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.46.2018.tde-26112018-080111
Application of cancer stem cells in improving therapeutics
Jain, S., Raza, K., Agrawal, A. K., & Vaidya, A. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-817846-1.00015-1
Marks, B. A., Choate, L. A., Sams, K. L., Zhu, L., Waidyaratne, G., Danko, C. G., & Coonrod, S. A. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.08.22.504845
Zheng, Y., Zhou, Y., Xia, H., Liang, W., Wei, X., & Zhou, J. (2025) · Gastrointestinal Tumors · doi:10.48130/git-0025-0001
Cao, M., Liu, Z., You, D., Pan, Y., & Zhang, Q. (2023) · Figshare · doi:10.6084/m9.figshare.22767311
Cao, M., Liu, Z., You, D., Pan, Y., & Zhang, Q. (2023) · Figshare · doi:10.6084/m9.figshare.22767314
Sun, X., Sun, Y., Li, J., Zhao, X., Shi, X., Gong, T., Pan, S., Zheng, Z., & Zhang, X. (2021) · Figshare · doi:10.6084/m9.figshare.14211342
Sun, X., Sun, Y., Li, J., Zhao, X., Shi, X., Gong, T., Pan, S., Zheng, Z., & Zhang, X. (2021) · Figshare · doi:10.6084/m9.figshare.14211339
Sun, X., Sun, Y., Li, J., Zhao, X., Shi, X., Gong, T., Pan, S., Zheng, Z., & Zhang, X. (2021) · Figshare · doi:10.6084/m9.figshare.14211336
Cao, M., Liu, Z., You, D., Pan, Y., & Zhang, Q. (2023) · Figshare · doi:10.6084/m9.figshare.22767308
Sun, X., Sun, Y., Li, J., Zhao, X., Shi, X., Gong, T., Pan, S., Zheng, Z., & Zhang, X. (2021) · Figshare · doi:10.6084/m9.figshare.14211345
Small cell lung cancer and cancer stem cell-like cells
Sarvi, S. (2014) · ERA
Metadata
- Authors
- Levina, V., Marrangoni, A., Wang, T., Parikh, S., Su, Y., Herberman, R., Lokshin, A., & Gorelik, E.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Levina, Vera
- Venue
- Cancer Research
- Published
- 2010-01-01
- Volume
- 70
- Issue
- 1
- Pages
- 338-346
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC4572892
- OpenAlex
- W2093146854
- Cited by
- 155
- References
- 48
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 6 · 2022: 8 · 2021: 13 · 2020: 5 · 2019: 7 · 2018: 10 · 2017: 9 · 2016: 9 · 2015: 9 · 2014: 16 · 2013: 18 · 2012: 17
- FWCI
- 6.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R21CA143736, R01CA098642, U01CA117452, R03CA136019, R01CA108990)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- lung cancer stem cells, non-small cell lung cancer, stem cell factor, CD117, autocrine signaling, imatinib, cisplatin, chemoresistance, tumor spheres, self-renewal, combination therapy
- MeSH terms
- Imatinib Mesylate, Antineoplastic Combined Chemotherapy Protocols, Benzamides, Carcinoma, Non-Small-Cell Lung, Cells, Cultured, Cisplatin, Flow Cytometry, Humans, Image Processing, Computer-Assisted, Lung Neoplasms, Piperazines, Pyrimidines, Neoplastic Stem Cells, Signal Transduction, Proto-Oncogene Proteins c-kit, Stem Cell Factor, Autocrine Communication
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