Research Status of Lung Cancer Stem Cell Markers_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

 LIUZhe-liang , XIAOGao-ming , CHENYue-jun , WUGuan-yu

The First Department of Thoracic Surgery, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, P. R. China;

Corresponding author：

LIUZhe-liang, Email: qdxyll@tom.com

Keywords：

Lung cancer; Lung cancer stem cell; Marker; Identification

DOI：

10.7507/1007-4848.20140152

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Lung cancers are highly heterogeneous and resistant to available therapeutic agents, with a five-year survival rate of less than 15%. Despite significant advances in our knowledge of the genetic alterations and aberrations in lung cancer, it has been difficult to determine the basis of lung cancer's heterogeneity and drug resistance. Cancer stem cell model has attracted a significant amount of attention in recent years as a viable explanation for the heterogeneity, drug resistance, dormancy, recurrence and metastasis of various tumors. At the same time, cancer stem cells have been relatively less characterized in lung cancers. This review summarizes the current understanding of lung cancer stem cells, including their molecular features and signaling pathways that drive their stemness. This review also discusses the prognosis of lung cancer and its relationship with lung cancer stem cell, in an effort to eradicate these cells to combat lung cancer.

Citation： LIUZhe-liang, XIAOGao-ming, CHENYue-jun, WUGuan-yu. Research Status of Lung Cancer Stem Cell Markers. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2014, 21(4): 537-541. doi: 10.7507/1007-4848.20140152 Copy

1.	Proctor RN. Tobacco and the global lung cancer epidemic. Nat Rev Cancer, 2001, 1 (1):82-86.
2.	Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin, 2005, 55 (2):74-108.
3.	Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin, 2012, 62 (1):10-29.
4.	Tong L, Spitz MR, Fueger JJ, et al. Lung carcinoma in former smokers. Cancer, 1996, 78 (5):1004-1010.
5.	Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin, 2008, 58 (2):71-96.
6.	Jemal A, Thun MJ, Ries LA, et al. Annual report to the nation on the status of cancer, 1975-2005, featuring trends in lung cancer, tobacco use, and tobacco control. J Natl Cancer Inst, 2008, 100 (23):1672-1694.
7.	Hanahan D, Weinberg RA. Hallmarks of cancer:the next generation. Cell, 2011, 144 (5):646-674.
8.	Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours:accumulating evidence and unresolved questions. Nat Rev Cancer, 2008, 8 (10):755-768.
9.	Clarke MF, Dick JE, Dirks PB, et al. Cancer stem cells--perspectives on current status and future directions:AACR Workshop on cancer stem cells. Cancer Res, 2006, 66 (19):9339-9344.
10.	Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med, 1997, 3 (7):730-737.
11.	Al-Hajj M, Wicha MS, Benito-Hernandez A, et al. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA, 2003, 100 (7):3983-3988.
12.	Medema JP.Cancer stem cells:the challenges ahead. Nat Cell Biol, 2013, 15 (4):338-344.
13.	Chen J, Li Y, Yu TS, et al. A restricted cell population propagates glioblastoma growth after chemotherapy. Nature, 2012, 488 (7412):522-526.
14.	Driessens G, Beck B, Caauwe A, et al. Defining the mode of tumour growth by clonal analysis. Nature, 2012, 488 (7412):527-530.
15.	Schepers AG, Snippert HJ, Stange DE, et al. Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas. Science, 2012, 337 (6095):730-735.
16.	Carney DN, Gazdar AF, Minna JD. Positive correlation between histological tumor involvement and generation of tumor cell colonies in agarose in specimens taken directly from patients with small-cell carcinoma of the lung. Cancer Res, 1980, 40 (6):1820-1823.
17.	Carney DN, Gazdar AF, Bunn PA Jr, et al. Demonstration of the stem cell nature of clonogenic tumor cells from lung cancer patients. Stem Cells, 1982, 1 (3):149-164.
18.	Goodell MA, Brose K, Paradis G, et al. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med, 1996, 183 (4):1797-1806.
19.	Golebiewska A, Brons NH, Bjerkvig R, et al. Critical appraisal of the side population assay in stem cell and cancer stem cell research. Cell Stem Cell, 2011, 8 (2):136-147.
20.	Ho MM, Ng AV, Lam S, et al. Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res, 2007, 67 (10):4827-4833.
21.	Salcido CD, Larochelle A, Taylor BJ, et al. Molecular characterisation of side population cells with cancer stem cell-like characteristics in small-cell lung cancer. Br J Cancer, 2010, 102 (11):1636-1644.
22.	Singh S, Trevino J, Bora-Singhal N, et al. EGFR/Src/Akt signaling modulates Sox2 expression and self-renewal of stem-like side-popula-tion cells in non-small cell lung cancer. Mol Cancer, 2012, 11:73-88.
23.	Singh S, Bora-Singhal N, Kroeger J, et al. βArrestin-1 and Mcl-1 modulate self-renewal growth of cancer stem-like side-population cells in non-small cell lung cancer. PLoS One, 2013, 8 (2):e55982.
24.	Perumal D, Singh S, Yoder SJ, et al. A novel five gene signature derived from stem-like side population cells predicts overall and recurrence-free survival in NSCLC. PLoS One, 2012, 7 (8):e43589.
25.	Alison MR, Guppy NJ, Lim SM, et al. Finding cancer stem cells:are aldehyde dehydrogenases fit for purpose? J Pathol, 2010, 222 (4):335-344.
26.	Patel M, Lu L, Zander DS, et al. ALDH1A1 and ALDH3A1 expression in lung cancers:correlation with histologic type and potential precursors. Lung Cancer, 2008, 59 (3):340-349.
27.	Sullivan JP, Spinola M, Dodge M, et al. Aldehyde dehydrogenase activity selects for lung adenocarcinoma stem cells dependent on notch signaling. Cancer Res, 2010, 70 (23):9937-9948.
28.	Okudela K, Woo T, Mitsui H, et al. Downregulation of ALDH1A1 expression in non-small cell lung carcinomas--its clinicopathologic and biological significance. Int J Clin Exp Pathol, 2013, 6 (1):1-12.
29.	Zhang WC, Shyh-Chang N, Yang H, et al. Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis. Cell, 2012, 148 (1-2):259-272.
30.	Mizrak D, Brittan M, Alison M. CD133:molecule of the moment. J Pathol, 2008, 214 (1):3-9.
31.	Keysar SB, Jimeno A. More than markers:biological significance of cancer stem cell-defining molecules. Mol Cancer Ther, 2010, 9 (9):2450-2457.
32.	Eramo A, Lotti F, Sette G, et al. Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ, 2008, 15 (3):504-514.
33.	Bertolini G, Roz L, Perego P, et al. Highly tumorigenic lung cancer CD133+ cells display stem-like features and are spared by cisplatin treatment. Proc Natl Acad Sci USA, 2009, 106 (38):16281-16286.
34.	Mizugaki H, Sakakibara-Konishi J, Kikuchi J, et al. CD133 expression:a potential prognostic marker for non-small cell lung cancers. Int J Clin Oncol, 2014, 19 (2):254-259.
35.	Shien K, Toyooka S, Ichimura K, et al. Prognostic impact of cancer stem cell-related markers in non-small cell lung cancer patients treated with induction chemoradiotherapy. Lung Cancer, 2012, 77 (1):162-167.
36.	Herpel E, Jensen K, Muley T, et al. The cancer stem cell antigens CD133, BCRP1/ABCG2 and CD117/c-KIT are not associated with prognosis in resected early-stage non-small cell lung cancer. Anticancer Res, 2011, 31 (12):4491-4500.
37.	Alamgeer M, Ganju V, Szczepny A, et al. The prognostic significance of aldehyde dehydrogenase 1 A1 (ALDH1A1) and CD133 expression in early stage non-small cell lung cancer. Thorax, 2013, 68 (12):1095-1104.
38.	Cortes-Dericks L, Galetta D, Spaggiari L, et al. High expression of octamer-binding transcription factor 4A, prominin-1 and aldehyde dehydrogenase strongly indicates involvement in the initiation of.
39.	lung adenocarcinoma resulting in shorter disease-free intervals. Eur J Cardiothorac Surg, 2012, 41 (6):e173-181.
40.	Du L, Wang H, He L, et al. CD44 is of functional importance for colorectal cancer stem cells. Clin Cancer Res, 2008, 14 (21):6751-6760.
41.	Shimada Y, Ishii G, Nagai K, et al. Expression of podoplanin, CD44, and p63 in squamous cell carcinoma of the lung. Cancer Sci, 2009, 100 (11):2054-2059.
42.	Bapat SA. Human ovarian cancer stem cells.Reproduction, 2010, 140 (1):33-41.
43.	Leung EL, Fiscus RR, Tung JW, et al. Non-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties.PLoS One, 2010, 5 (11):e14062.
44.	Lu ZQ, Li HG, Zhang HZ, et al. Expression and significance of CD44 (+)ESA (+) CD24 (-/low), stem cell markers for breast cancer, in non-small-cell lung carcinoma. Ai Zheng, 2008, 27 (6):575-579.
45.	Lin WM, Karsten U, Goletz S, et al. Expression of CD176 (Thomsen-Friedenreich antigen) on lung, breast and liver cancer-initiating cells.Int J Exp Pathol, 2011, 92 (2):97-105.
46.	Karoubi G, Cortes-Dericks L, Gugger M, et al. Atypical expression and distribution of embryonic stem cell marker, OCT4, in human lung adenocarcinoma.J Surg Oncol, 2010, 102 (6):689-698.
47.	Zhang X, Han B, Huang J, et al. Prognostic significance of OCT4 expression in adenocarcinoma of the lung. Jpn J Clin Oncol, 2010, 40 (10):961-966.
48.	Zhang XY, Zheng BQ, Han BH, et al. Lung adenocarcinoma stem cell phenotypes and their correlation with patient prognosis, 2009, 31 (11):836-840.
49.	Sholl LM, Long KB, Hornick JL. Sox2 expression in pulmonary non-small cell and neuroendocrine carcinomas.Appl Immunohistochem Mol Morphol, 2010, 18 (1):55-61.
50.	Hussenet T, du Manoir S. SOX2 in squamous cell carcinoma:amplifying a pleiotropic oncogene along carcinogenesis.Cell Cycle, 2010, 9 (8):1480-1486.

1. Proctor RN. Tobacco and the global lung cancer epidemic. Nat Rev Cancer, 2001, 1 (1):82-86.
2. Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin, 2005, 55 (2):74-108.
3. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin, 2012, 62 (1):10-29.
4. Tong L, Spitz MR, Fueger JJ, et al. Lung carcinoma in former smokers. Cancer, 1996, 78 (5):1004-1010.
5. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin, 2008, 58 (2):71-96.
6. Jemal A, Thun MJ, Ries LA, et al. Annual report to the nation on the status of cancer, 1975-2005, featuring trends in lung cancer, tobacco use, and tobacco control. J Natl Cancer Inst, 2008, 100 (23):1672-1694.
7. Hanahan D, Weinberg RA. Hallmarks of cancer:the next generation. Cell, 2011, 144 (5):646-674.
8. Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours:accumulating evidence and unresolved questions. Nat Rev Cancer, 2008, 8 (10):755-768.
9. Clarke MF, Dick JE, Dirks PB, et al. Cancer stem cells--perspectives on current status and future directions:AACR Workshop on cancer stem cells. Cancer Res, 2006, 66 (19):9339-9344.
10. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med, 1997, 3 (7):730-737.
11. Al-Hajj M, Wicha MS, Benito-Hernandez A, et al. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA, 2003, 100 (7):3983-3988.
12. Medema JP.Cancer stem cells:the challenges ahead. Nat Cell Biol, 2013, 15 (4):338-344.
13. Chen J, Li Y, Yu TS, et al. A restricted cell population propagates glioblastoma growth after chemotherapy. Nature, 2012, 488 (7412):522-526.
14. Driessens G, Beck B, Caauwe A, et al. Defining the mode of tumour growth by clonal analysis. Nature, 2012, 488 (7412):527-530.
15. Schepers AG, Snippert HJ, Stange DE, et al. Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas. Science, 2012, 337 (6095):730-735.
16. Carney DN, Gazdar AF, Minna JD. Positive correlation between histological tumor involvement and generation of tumor cell colonies in agarose in specimens taken directly from patients with small-cell carcinoma of the lung. Cancer Res, 1980, 40 (6):1820-1823.
17. Carney DN, Gazdar AF, Bunn PA Jr, et al. Demonstration of the stem cell nature of clonogenic tumor cells from lung cancer patients. Stem Cells, 1982, 1 (3):149-164.
18. Goodell MA, Brose K, Paradis G, et al. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med, 1996, 183 (4):1797-1806.
19. Golebiewska A, Brons NH, Bjerkvig R, et al. Critical appraisal of the side population assay in stem cell and cancer stem cell research. Cell Stem Cell, 2011, 8 (2):136-147.
20. Ho MM, Ng AV, Lam S, et al. Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res, 2007, 67 (10):4827-4833.
21. Salcido CD, Larochelle A, Taylor BJ, et al. Molecular characterisation of side population cells with cancer stem cell-like characteristics in small-cell lung cancer. Br J Cancer, 2010, 102 (11):1636-1644.
22. Singh S, Trevino J, Bora-Singhal N, et al. EGFR/Src/Akt signaling modulates Sox2 expression and self-renewal of stem-like side-popula-tion cells in non-small cell lung cancer. Mol Cancer, 2012, 11:73-88.
23. Singh S, Bora-Singhal N, Kroeger J, et al. βArrestin-1 and Mcl-1 modulate self-renewal growth of cancer stem-like side-population cells in non-small cell lung cancer. PLoS One, 2013, 8 (2):e55982.
24. Perumal D, Singh S, Yoder SJ, et al. A novel five gene signature derived from stem-like side population cells predicts overall and recurrence-free survival in NSCLC. PLoS One, 2012, 7 (8):e43589.
25. Alison MR, Guppy NJ, Lim SM, et al. Finding cancer stem cells:are aldehyde dehydrogenases fit for purpose? J Pathol, 2010, 222 (4):335-344.
26. Patel M, Lu L, Zander DS, et al. ALDH1A1 and ALDH3A1 expression in lung cancers:correlation with histologic type and potential precursors. Lung Cancer, 2008, 59 (3):340-349.
27. Sullivan JP, Spinola M, Dodge M, et al. Aldehyde dehydrogenase activity selects for lung adenocarcinoma stem cells dependent on notch signaling. Cancer Res, 2010, 70 (23):9937-9948.
28. Okudela K, Woo T, Mitsui H, et al. Downregulation of ALDH1A1 expression in non-small cell lung carcinomas--its clinicopathologic and biological significance. Int J Clin Exp Pathol, 2013, 6 (1):1-12.
29. Zhang WC, Shyh-Chang N, Yang H, et al. Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis. Cell, 2012, 148 (1-2):259-272.
30. Mizrak D, Brittan M, Alison M. CD133:molecule of the moment. J Pathol, 2008, 214 (1):3-9.
31. Keysar SB, Jimeno A. More than markers:biological significance of cancer stem cell-defining molecules. Mol Cancer Ther, 2010, 9 (9):2450-2457.
32. Eramo A, Lotti F, Sette G, et al. Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ, 2008, 15 (3):504-514.
33. Bertolini G, Roz L, Perego P, et al. Highly tumorigenic lung cancer CD133+ cells display stem-like features and are spared by cisplatin treatment. Proc Natl Acad Sci USA, 2009, 106 (38):16281-16286.
34. Mizugaki H, Sakakibara-Konishi J, Kikuchi J, et al. CD133 expression:a potential prognostic marker for non-small cell lung cancers. Int J Clin Oncol, 2014, 19 (2):254-259.
35. Shien K, Toyooka S, Ichimura K, et al. Prognostic impact of cancer stem cell-related markers in non-small cell lung cancer patients treated with induction chemoradiotherapy. Lung Cancer, 2012, 77 (1):162-167.
36. Herpel E, Jensen K, Muley T, et al. The cancer stem cell antigens CD133, BCRP1/ABCG2 and CD117/c-KIT are not associated with prognosis in resected early-stage non-small cell lung cancer. Anticancer Res, 2011, 31 (12):4491-4500.
37. Alamgeer M, Ganju V, Szczepny A, et al. The prognostic significance of aldehyde dehydrogenase 1 A1 (ALDH1A1) and CD133 expression in early stage non-small cell lung cancer. Thorax, 2013, 68 (12):1095-1104.
38. Cortes-Dericks L, Galetta D, Spaggiari L, et al. High expression of octamer-binding transcription factor 4A, prominin-1 and aldehyde dehydrogenase strongly indicates involvement in the initiation of.
39. lung adenocarcinoma resulting in shorter disease-free intervals. Eur J Cardiothorac Surg, 2012, 41 (6):e173-181.
40. Du L, Wang H, He L, et al. CD44 is of functional importance for colorectal cancer stem cells. Clin Cancer Res, 2008, 14 (21):6751-6760.
41. Shimada Y, Ishii G, Nagai K, et al. Expression of podoplanin, CD44, and p63 in squamous cell carcinoma of the lung. Cancer Sci, 2009, 100 (11):2054-2059.
42. Bapat SA. Human ovarian cancer stem cells.Reproduction, 2010, 140 (1):33-41.
43. Leung EL, Fiscus RR, Tung JW, et al. Non-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties.PLoS One, 2010, 5 (11):e14062.
44. Lu ZQ, Li HG, Zhang HZ, et al. Expression and significance of CD44 (+)ESA (+) CD24 (-/low), stem cell markers for breast cancer, in non-small-cell lung carcinoma. Ai Zheng, 2008, 27 (6):575-579.
45. Lin WM, Karsten U, Goletz S, et al. Expression of CD176 (Thomsen-Friedenreich antigen) on lung, breast and liver cancer-initiating cells.Int J Exp Pathol, 2011, 92 (2):97-105.
46. Karoubi G, Cortes-Dericks L, Gugger M, et al. Atypical expression and distribution of embryonic stem cell marker, OCT4, in human lung adenocarcinoma.J Surg Oncol, 2010, 102 (6):689-698.
47. Zhang X, Han B, Huang J, et al. Prognostic significance of OCT4 expression in adenocarcinoma of the lung. Jpn J Clin Oncol, 2010, 40 (10):961-966.
48. Zhang XY, Zheng BQ, Han BH, et al. Lung adenocarcinoma stem cell phenotypes and their correlation with patient prognosis, 2009, 31 (11):836-840.
49. Sholl LM, Long KB, Hornick JL. Sox2 expression in pulmonary non-small cell and neuroendocrine carcinomas.Appl Immunohistochem Mol Morphol, 2010, 18 (1):55-61.
50. Hussenet T, du Manoir S. SOX2 in squamous cell carcinoma:amplifying a pleiotropic oncogene along carcinogenesis.Cell Cycle, 2010, 9 (8):1480-1486.

Previous Article
Risk Factor Analysis for Solitary Pulmonary Nodules between Benign and Malignant
Next Article
Left Ventricular Reconstruction:from Anatomy to Surgery

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Research Status of Lung Cancer Stem Cell Markers

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content