title: Cancer stem cells and cisplatin-resistant cells isolated from non-small-lung cancer cell lines constitute related cell populations.
abstract: Lung cancer is the top cause of cancer-related deceases. One of the reasons is the development of resistance to the chemotherapy treatment. In particular, cancer stem cells (CSCs), can escape treatment and regenerate the bulk of the tumor. In this article, we describe a comparison between cancer cells resistant to cisplatin and CSCs, both derived from the non-small-cell lung cancer cell lines H460 and A549. Cisplatin-resistant cells were obtained after a single treatment with the drug. CSCs were isolated by culture in defined media, under nonadherent conditions. The isolated CSCs were clonogenic, could be differentiated into adherent cells and were less sensitive to cisplatin than the original cells. Cisplatin resistant and CSCs were able to generate primary tumors and to metastasize when injected into immunodeficient Nu/Nu mice, although they formed smaller tumors with a larger latency than untreated cells. Notably, under appropriated proportions, CSCs synergized with differentiated cells to form larger tumors. CSCs also showed increased capacity to induce angiogenesis in Nu/Nu mice. Conversely, H460 cisplatin-resistant cells showed increased tendency to develop bone metastasis. Gene expression analysis showed that several genes involved in tumor development and metastasis (EGR1, COX2, MALAT1, AKAP12, ADM) were similarly induced in CSC and cisplatin-resistant H460 cells, in agreement with a close similarity between these two cell populations. Cells with the characteristic growth properties of CSCs were also isolated from surgical samples of 18 out of 44 lung cancer patients. A significant correlation (P = 0.028) was found between the absence of CSCs and cisplatin sensitivity.
authors: Instituto de Investigaciones Biomédicas CSIC/UAM, Biomarkers and Experimental Therapeutics in Cancer, IdiPAZ, Spain.
authors: Blanca D
authors: BD
authors: Lopez-Ayllon
authors: Veronica
authors: V
authors: Moncho-Amor
authors: Ander
authors: A
authors: Abarrategi
authors: Inmaculada
authors: I
authors: Ibañez de Cáceres
authors: Javier
authors: J
authors: Castro-Carpeño
authors: Cristobal
authors: C
authors: Belda-Iniesta
authors: Rosario
authors: R
authors: Perona
authors: Leandro
authors: L
authors: Sastre
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D002945:Cisplatin / Q000494:pharmacology*; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D009389:Neovascularization, Pathologic; D014410:Tumor Stem Cell Assay
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin
keywords: Cancer stem cells; NSCLC; cancer-initiating cells; cisplatin resistance; lung cancer