title: Isolation of cancer stem like cells from human adenosquamous carcinoma of the lung supports a monoclonal origin from a multipotential tissue stem cell.
abstract: There is increasing evidence that many solid tumors are hierarchically organized with the bulk tumor cells having limited replication potential, but are sustained by a stem-like cell that perpetuates the tumor. These cancer stem cells have been hypothesized to originate from transformation of adult tissue stem cells, or through re-acquisition of stem-like properties by progenitor cells. Adenosquamous carcinoma (ASC) is an aggressive type of lung cancer that contains a mixture of cells with squamous (cytokeratin 5+) and adenocarcinoma (cytokeratin 7+) phenotypes. The origin of these mixtures is unclear as squamous carcinomas are thought to arise from basal cells in the upper respiratory tract while adenocarcinomas are believed to form from stem cells in the bronchial alveolar junction. We have isolated and characterized cancer stem-like populations from ASC through application of selective defined culture medium initially used to grow human lung stem cells. Homogeneous cells selected from ASC tumor specimens were stably expanded in vitro. Primary xenografts and metastatic lesions derived from these cells in NSG mice fully recapitulate both the adenocarcinoma and squamous features of the patient tumor. Interestingly, while the CSLC all co-expressed cytokeratins 5 and 7, most xenograft cells expressed either one, or neither, with <10% remaining double positive. We also demonstrated the potential of the CSLC to differentiate to multi-lineage structures with branching lung morphology expressing bronchial, alveolar and neuroendocrine markers in vitro. Taken together the properties of these ASC-derived CSLC suggests that ASC may arise from a primitive lung stem cell distinct from the bronchial-alveolar or basal stem cells.
authors: MacroGenics, Inc., South San Francisco, California, United States of America.
authors: Jennie P
authors: JP
authors: Mather
authors: Penelope E
authors: PE
authors: Roberts
authors: Zhuangyu
authors: Z
authors: Pan
authors: Francine
authors: F
authors: Chen
authors: Jeffrey
authors: J
authors: Hooley
authors: Peter
authors: P
authors: Young
authors: Xiaolin
authors: X
authors: Xu
authors: Douglas H
authors: DH
authors: Smith
authors: Ann
authors: A
authors: Easton
authors: Panjing
authors: P
authors: Li
authors: Ezio
authors: E
authors: Bonvini
authors: Scott
authors: S
authors: Koenig
authors: Paul A
authors: PA
authors: Moore
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000378:metabolism / Q000473:pathology; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001980:Bronchi / Q000378:metabolism / Q000473:pathology; D018196:Carcinoma, Adenosquamous / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002999:Clone Cells; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D053555:Keratin-5 / Q000235:genetics* / Q000378:metabolism; D053552:Keratin-7 / Q000235:genetics* / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology; D014183:Transplantation, Heterologous
chemical_list: D014408:Biomarkers, Tumor; D053555:Keratin-5; D053552:Keratin-7