title: Is repetitive wounding and bone marrow-derived stem cell mediated-repair an etiology of lung cancer development and dissemination?
abstract: The prevailing view of lung cancer is multi-step progression of normal cells into cancer cells through gain of function oncogenes coupled with loss of tumor suppressor genes. This progression of genetic damage ultimately results in the hallmarks of cancer. This theory has strong support from studies finding genetic damage in early stage preneoplastic lesions in lung epithelial cells from current or former smokers. This paper discusses an alternate theory that lung cancer is a bone marrow stem cell derived disease. Chronic cigarette smoking results in lung inflammation and epithelial damage that activates a chronic wound repair program. Recent studies have demonstrated that ability of bone marrow derived stem cells to respond to epithelial wounding and contribute to epithelial repair. The identification of cancer stem cells that are distinct from the bulk tumor cells through their ability of self-renewal may suggest that such cells are important in the development of lung cancer. The evidence supporting the hypothesis along with its implications are discussed. Confirmation of the hypothesis would suggest that the transition time from a normal cell to overt cancer cell may be much shorter than that based on the multi-step cancer progression model. Additionally, if wounding in other organs is a beacon that attracts bone marrow derived tumor cells, efforts to ameliorate areas of epithelial injury and compensatory wounding may block bone marrow derived tumor cell homing, aberrant repair, and metastasis. Finally, a bone marrow derived lung cancer stem cell would require stem cell poisons for cure.
authors.affiliation: The H. Lee Moffitt Cancer Center & Research Institute, Department of Interdisciplinary Oncology, University of South Florida College of Medicine, MRC3 East, Tampa, FL 33612-9497, United States. hauraeb@moffitt.usf.edu
authors.forename: Eric B
authors.initials: EB
authors.lastname: Haura
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology* / Q000473:pathology; D008954:Models, Biological; D009362:Neoplasm Metastasis / Q000503:physiopathology; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014947:Wounds and Injuries / Q000503:physiopathology*