CD133-Positive Cells from Non-Small Cell Lung Cancer Show Distinct Sensitivity to Cisplatin and Afatinib

详细信息    查看全文

• 作者：Angela Alama ; Rosaria Gangemi…
• 关键词：NSCLC ; CD133 ; EpCAM ; Cisplatin ; Afatinib ; Drug ; resistance
• 刊名：Archivum Immunologiae et Therapiae Experimentalis
• 出版年：2015
• 出版时间：June 2015
• 年：2015
• 卷：63
• 期：3
• 页码：207-214
• 全文大小：1,032 KB
• 参考文献：Abhold EL, Kiang A, Rahimy E et al (2012) EGFR kinase promotes acquisition of stem cell-like properties: a potential therapeutic target in head and neck squamous cell carcinoma stem cells. PLoS One 2:e32459View Article
  Alama A, Orengo AM, Ferrini S et al (2012) Targeting cancer-initiating cell drug-resistance: a roadmap to a new-generation of cancer therapies? Drug Discov Today 17:435-42View Article PubMed
  Bertolini G, Roz L, Perego P et al (2009) Highly tumorigenic lung cancer CD133 cells display stem-like features and are spared by cisplatin treatment. Proc Natl Acad Sci USA 106:16281-6286View Article PubMed Central PubMed
  Chang A (2011) Chemotherapy, chemoresistance and the changing treatment landscape for NSCLC. Lung Cancer 71:3-0View Article PubMed
  Chen S, Huo X, Lin Y et al (2010) Association of MDR1 and ERCC1 polymorphisms with response and toxicity to cisplatin-based chemotherapy in non-small-cell lung cancer patients. Int J Hyg Environ Health 213:140-45View Article PubMed
  Chen Y, Yu D, Zhang H et al (2012) CD133(+)EpCAM(+) phenotype possesses more characteristics of tumor initiating cells in hepatocellular carcinoma Huh7 cells. Int J Biol Sci 8:992-004View Article PubMed Central PubMed
  Cufer T, Ovcaricek T, O’Brien ME (2013) Systemic therapy of advanced non-small cell lung cancer: major-developments of the last 5-years. Eur J Cancer 49:1216-225View Article PubMed
  Favoni RE, Alama A (2013) Preclinical strategies targeted at non-small-cell lung cancer signalling pathways with striking translational fallout. Drug Discov Today 18:11-4View Article PubMed
  Ferlay J, Shin HR, Bray F et al (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893-917View Article PubMed
  Galvani E, Giovannetti E, Saccani F et al (2013) Molecular mechanisms underlying the antitumor activity of 3-aminopropanamide irreversible inhibitors of the epidermal growth factor receptor in non–small cell lung cancer. Neoplasia 15:61-2View Article PubMed Central PubMed
  Gottschling S, Herpel E, Eberhardt WE et al (2012) The gefitinib long-term responder (LTR)—a cancer stem-like cell story? Insights from molecular analyses of German long-term responders treated in the IRESSA expanded access program (EAP). Lung Cancer 77:183-91View Article PubMed
  Levina V, Marrangoni AM, DeMarco R et al (2008) Drug-selected human lung cancer stem cells: cytokine net-work, tumorigenic and metastatic properties. PLoS One 3:e3077View Article PubMed Central PubMed
  Li D, Ambrogio L, Shimamura T et al (2008) BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene 27:4702-711View Article PubMed Central PubMed
  Maugeri-Saccà M, Vigneri P, De Maria R (2011) Cancer stem cells and chemosensitivity. Clin Cancer Res 17:4942-947View Article PubMed
  Mazzoleni S, Politi LS, Pala M et al (2010) Epidermal growth factor receptor expression identifies functionally and molecularly distinct tumor-initiating cells in human glioblastoma multiforme and is required for gliomagenesis. Cancer Res 70:7500-513View Article PubMed
  Munz M, Baeuerle PA, Gires O (2009) The emerging role of EpCAM in cancer and stem cell signaling. Cancer Res 69:5627-629View Article PubMed
  Neuzil J, Stantic M, Zobalova R et al (2007) Tumor-initiating cells vs. cancer ‘stem-cells and CD133: what’s in the name? Biochem Biophys Res Commun 355:855-59View Article PubMed
  Nguyen KS, Kobayashi S, Costa DB (2009) Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancers dependent on the epidermal growth factor receptor pathway. Clin Lung Cancer 10:281-89View Article PubMed Central PubMed
  Nguyen LV, Vanner R, Dirks P et al (2012) Cancer stem cells: an evolving concept. Nat Rev Cancer 12:133-43PubMed
  Ono M, Kuwano M (2006) Molecular mechanisms of epidermal growth factor receptor (EGFR) activation and response to gefitinib and other EGFR-targeting drugs. Clin Cancer Res 12:7242-251View Article PubMed
  Pao W, Miller V, Zakowski M et al (2004) EGF receptor gene mutations are common in lung cancers from “never smokers-and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci USA 101:13306-3311View Article PubMed Central PubMed
  Peacock CD, Watkins N (2008) Cancer stem cells and the ontogeny of lung cancer. J Clin Oncol 26:2883-889View Article PubMed Central PubMed
  Singh S, Trevino J, Bora-Singhal N et al (2012) EGFR/Src/Akt signaling modulates Sox2 expression and self-renewal of stem-like side-population cells in non-small cell lung cancer. Mol Cancer 11:73View Article PubMed Central PubMed
  Skirecki T, Hoser G, Kawiak J et al (2014) Flow cytometric analysis of CD133- and EpCAM-positive cells in the peripheral blood of patients with lung cancer. Arch Immunol Ther Exp 62:67-5View Article
  Tan DS, Gerlinger M, Teh BT et al (2010) Anti-cancer dr
• 作者单位：Angela Alama (1)
  Rosaria Gangemi (2)
  Silvano Ferrini (2)
  Gaia Barisione (2)
  Anna Maria Orengo (2)
  Mauro Truini (3)
  Maria Giovanna Dal Bello (1)
  Francesco Grossi (1)
  
  1. Lung Cancer Unit, IRCCS A.O.U. San Martino-IST, National Institute for Cancer Research, Largo Rosanna Benzi, 10, 16132, Genoa, Italy
  2. Laboratory of Bio-therapy, IRCCS A.O.U. San Martino-IST, National Institute for Cancer Research, Largo Rosanna Benzi, 10, 16132, Genoa, Italy
  3. Department of Pathology, IRCCS A.O.U. San Martino-IST, National Institute for Cancer Research, Largo Rosanna Benzi, 10, 16132, Genoa, Italy
  
• 刊物主题：Immunology; Pharmacology/Toxicology;
• 出版者：Springer Basel
• ISSN：1661-4917

文摘

The standard of care for advanced non-small cell lung cancer (NSCLC) consists in cisplatin-combination chemotherapy. In patients bearing tumors with activating mutations of the epidermal growth factor receptor (EGFR), the inhibition of the EGFR intracellular tyrosine kinase can induce up to 80?% response rates. However, both therapeutic strategies will eventually lead to recurrent disease due to the development of drug resistance. The identification of rare cancer stem-like cells able to repopulate the tumor, after failure to standard treatment modalities, has led to characterize these cells as potential therapeutic targets. This article will address the role of the CD133/EpCAM stem cell-related markers and explore cell sensitivity to cisplatin and to the EGFR-tyrosine kinase inhibitor, afatinib. Three human NSCLC cell lines, one wild-type (A549) and two harboring EGFR mutations (H1650 and H1975), as well as 20 NSCLC primary cultures, were grown in non-differentiating culture conditions for stem cell enrichment. Flow-cytometry analyses of CD133 and EpCAM and cell sensitivity to cisplatin and afatinib were performed. Moreover, the expression of activated EGFR was assessed by Western blot. The cell lines and primary cultures grown in non-differentiating culture conditions were enriched with CD133/EpCAM-positive cells and were significantly more resistant to cisplatin and more sensitive to afatinib as compared to the differentiated counterpart. In addition, increased EGFR-phosphorylation in non-differentiated cultures was observed. The present findings suggest that afatinib might be beneficial for patients bearing tumors with constitutively activated EGFR, to target chemo-resistant CD133/EpCAM-positive cancer stem cells.