Airway stem cells and lung cancer

Abstract

Lung cancer is the biggest cancer killer in the UK and despite recent therapeutic advances there is a desperate need for new therapies to improve outcomes from this devastating disease. Through defining the spatial location of the airway epithelial stem or progenitor cell populations and their mechanisms of maintenance and repair of the epithelium it is becoming clear that these populations are situated at areas corresponding to those involved in lung cancer initiation. We explore the evidence for stem cells being the cancer initiator cell and for a 'lung cancer stem cell' within tumours that may be the cause of resistance to current therapies.

Diversity of Epithelial Stem Cell Types in Adult Lung

“…In this regard, a distinct phenotype of lung cancer shares the characteristics with the corresponding regional stem/progenitor cell population responsible for the injury repair of this area [3, 68, 71, 76–78]. This hypothesis is supported in part by findings from animal models of induced lung cancers, where lung cancers originated from resident stem cells, and the most originating sites of different types of lung cancer are correlated with distinct airway stem cell niches (Figure 2) [24, 33, 34, 79, 80]. In this context, the adenocarcinomas are characterized with expression of CK14, transcription factor Nkx2.1 (TTF1), CCSP, and SPC and arose from the BADJ in murine model, suggesting that club cells or AEC II cells stem/progenitor cells may be the initiating cells for adenocarcinomas in distal lung [3, 70, 71, 78, 81, 82].…”

A possible role of stem cells in nasal polyposis

“…Following this concept, regenerative processes of the upper and lower airways may also involve stem cells. Indeed, the current literature implies stem cells to be involved in regenerative processes in lower airways . In the lung, different populations of epithelial cells function as adult stem cells, defined by their self‐renewal properties and phenotypic changes in response to tissue damage .…”

Progenitor Cells in Proximal Airway Epithelial Development and Regeneration

“…Those studying cancer initiation have also promoted the hypothesis that airway-specific progenitors possess inherent defenses against damage. Based on these drug resistant tendencies, some in the field suspect lung cancers result from pathological changes in the microenvironment of airway stem cells [Succony and Janes, 2014). Although the existence of "cancer stem cells" is still controversial, this area merits further study as many findings indicate that airway progenitor cells possess cell-specific defensive mechanisms that may give them an evolutionary advantage during tumor progression.…”