Abstract
In all tissues of the body, epithelial stem cells play a critical role in directing tissue generation and organogenesis during development, in repair following injury, and in regeneration following tissue loss. In the highly branched and compartmentalized lung, homeostatic maintenance and responses to injury are driven by multiple, different, resident stem/progenitor cell populations. Consistent or repeated failure of lung stem/progenitor cell function in the absence of oncogenic mutation can result in lung epithelial injury and chronic lung disease, which carries high levels of morbidity and mortality worldwide. Lung stem/progenitor cell dysfunction due to oncogenic mutation drives the development of lung cancer, which poses a highly significant risk to human health and constitutes the most common form of cancer death worldwide. Cancer is identified by its cell of origin, namely the type of cell that incurred the first oncogenic mutation. Over the last two decades, multiple studies have postulated that stem cells themselves, or cells that have de-differentiated and acquired stem-like properties, may serve as the originating cancer cell. Like stem cells that drive development, tissue repair, and regeneration, cancer stem cells are characterized by properties of self-renewal and the ability to produce differentiated progeny. These characteristics are also hypothesized to underlie the role cancer stem cells play in the propagation and spread of the disease. Lung cancer stem cells are putatively derived from several possible cell sources, with evidence coming from pathological and genomic analyses of human tumors as well as molecular and cellular analyses of transgenic mouse models. The stem cell-like resistance to injury and proliferative potential of the stem cells of the distal lung, including airway club cells, bronchioalveolar stem cells and alveolar epithelial type 2 cells, make each of these distinct populations potential reservoirs for lung cancer stem cells.
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Abbreviations
- AAH:
-
Atypical adenomatous hyperplasia’s
- AEC1/1:
-
Alveolar epithelial cell 1/2
- BASC:
-
Bronchioalveolar stem cell
- CC10:
-
Clara cell 10 kDa
- CCSP:
-
Clara cell secretory protein
- COPD:
-
Chronic obstructive pulmonary disease
- CSC:
-
Cancer stem cell
- EGFR:
-
Epithelial growth factor receptor
- Hh:
-
Hedgehog
- IPF:
-
Idiopathic pulmonary hypertension
- Krt:
-
Keratin
- NE:
-
Neuroendocrine cell
- NSCLC:
-
None small cell lung cancer
- OB:
-
Obliterative bronchitis
- SCGB1A1:
-
Secretoglobin family 1A member 1 protein
- SCLC:
-
Small cell lung cancer
- SFTPC:
-
Surfactant protein C
- TTF-1:
-
Thyroid transcription factor 1 (aka NKx2.1)
- Trp63:
-
Tumor repressor protein 63
- WNT:
-
Wingless-related integration site
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Acknowledgment
This work was partially supported by NIH grant R01 HL 065352 to B.D., by a training grant from the California Institute of Regenerative Medicine and by an endowment from the Pasadena Guild.
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Hiatt, M., Garcia, O., Lundin, A., Driscoll, B. (2015). Bronchioalveolar Stem Cells in Cancer. In: Firth, A., Yuan, JJ. (eds) Lung Stem Cells in the Epithelium and Vasculature. Stem Cell Biology and Regenerative Medicine. Springer, Cham. https://doi.org/10.1007/978-3-319-16232-4_4
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