1. Identification and expansion of the tumorigenic lung cancer stem cell population
- Author
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Cesare Peschle, R De Maria, Fiorenza Lotti, A. Di Virgilio, Luigi Ruco, Marco Biffoni, Giovanni Sette, Emanuela Pilozzi, Concetta Conticello, and Adriana Eramo
- Subjects
cancer stem cells ,Lung Neoplasms ,Cellular differentiation ,Drug Resistance ,tumor sphere ,Mice, SCID ,Mice ,Epidermal growth factor ,Carcinoma, Non-Small-Cell Lung ,Tumor Cells, Cultured ,AC133 Antigen ,Carcinoma, Small Cell ,Non-Small-Cell Lung ,education.field_of_study ,Cultured ,stem cell markers ,Cell Differentiation ,CD ,Tumor Cells ,Haematopoiesis ,Phenotype ,Neoplastic Stem Cells ,Female ,Population ,Biology ,SCID ,Cancer stem cell ,Settore MED/04 - PATOLOGIA GENERALE ,Antigens, CD ,medicine ,cd133 ,lung cancer ,pulmonary stem cells ,Animals ,Humans ,Antigens ,Lung cancer ,education ,Molecular Biology ,Glycoproteins ,Lineage markers ,Carcinoma ,Cancer ,Cell Biology ,Small Cell ,medicine.disease ,Xenograft Model Antitumor Assays ,Drug Resistance, Neoplasm ,Peptides ,Immunology ,Cancer research ,Neoplasm - Abstract
Lung carcinoma is often incurable and remains the leading cancer killer in both men and women. Recent evidence indicates that tumors contain a small population of cancer stem cells that are responsible for tumor maintenance and spreading. The identification of the tumorigenic population that sustains lung cancer may contribute significantly to the development of effective therapies. Here, we found that the tumorigenic cells in small cell and non-small cell lung cancer are a rare population of undifferentiated cells expressing CD133, an antigen present in the cell membrane of normal and cancer-primitive cells of the hematopoietic, neural, endothelial and epithelial lineages. Lung cancer CD133(+) cells were able to grow indefinitely as tumor spheres in serum-free medium containing epidermal growth factor and basic fibroblast growth factor. The injection of 10(4) lung cancer CD133(+) cells in immunocompromised mice readily generated tumor xenografts phenotypically identical to the original tumor. Upon differentiation, lung cancer CD133(+) cells acquired the specific lineage markers, while loosing the tumorigenic potential together with CD133 expression. Thus, lung cancer contains a rare population of CD133(+) cancer stem-like cells able to self-renew and generates an unlimited progeny of non-tumorigenic cells. Molecular and functional characterization of such a tumorigenic population may provide valuable information to be exploited in the clinical setting.
- Published
- 2007