title: Identification and characterization of cells with cancer stem cell properties in human primary lung cancer cell lines.
abstract: Lung cancer (LC) with its different subtypes is generally known as a therapy resistant cancer with the highest morbidity rate worldwide. Therapy resistance of a tumor is thought to be related to cancer stem cells (CSCs) within the tumors. There have been indications that the lung cancer is propagated and maintained by a small population of CSCs. To study this question we established a panel of 15 primary lung cancer cell lines (PLCCLs) from 20 fresh primary tumors using a robust serum-free culture system. We subsequently focused on identification of lung CSCs by studying these cell lines derived from 4 representative lung cancer subtypes such as small cell lung cancer (SCLC), large cell carcinoma (LCC), squamous cell carcinoma (SCC) and adenocarcinoma (AC). We identified a small population of cells strongly positive for CD44 (CD44(high)) and a main population which was either weakly positive or negative for CD44 (CD44(low/-)). Co-expression of CD90 further narrowed down the putative stem cell population in PLCCLs from SCLC and LCC as spheroid-forming cells were mainly found within the CD44(high)CD90(+) sub-population. Moreover, these CD44(high)CD90(+) cells revealed mesenchymal morphology, increased expression of mesenchymal markers N-Cadherin and Vimentin, increased mRNA levels of the embryonic stem cell related genes Nanog and Oct4 and increased resistance to irradiation compared to other sub-populations studied, suggesting the CD44(high)CD90(+) population a good candidate for the lung CSCs. Both CD44(high)CD90(+) and CD44(high)CD90(-) cells in the PLCCL derived from SCC formed spheroids, whereas the CD44(low/-) cells were lacking this potential. These results indicate that CD44(high)CD90(+) sub-population may represent CSCs in SCLC and LCC, whereas in SCC lung cancer subtype, CSC potentials were found within the CD44(high) sub-population.
authors.affiliation: Department of Immunology, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, Oslo, Norway.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Quanli
authors.initials: Q
authors.lastname: Gao
authors.forename: Zhenhe
authors.initials: Z
authors.lastname: Suo
authors.forename: Else
authors.initials: E
authors.lastname: Munthe
authors.forename: Steinar
authors.initials: S
authors.lastname: Solberg
authors.forename: Liwei
authors.initials: L
authors.lastname: Ma
authors.forename: Mengyu
authors.initials: M
authors.lastname: Wang
authors.forename: Nomdo Anton Christiaan
authors.initials: NA
authors.lastname: Westerdaal
authors.forename: Gunnar
authors.initials: G
authors.lastname: Kvalheim
authors.forename: Gustav
authors.initials: G
authors.lastname: Gaudernack
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D018287:Carcinoma, Large Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D016130:Immunophenotyping; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D000071317:Nanog Homeobox Protein; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D055752:Small Cell Lung Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018800:Thy-1 Antigens / Q000235:genetics / Q000378:metabolism; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C050361:CDH2 protein, human; D015820:Cadherins; D018398:Homeodomain Proteins; D018960:Hyaluronan Receptors; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D018800:Thy-1 Antigens; D014746:Vimentin