Lung cancer stem cells: Progress and prospects

Abstract

Epithelial stem cells are critical for tissue generation during development and for repair following injury. In both gestational and postnatal stages, the highly branched and compartmentalized organization of the lung is maintained by multiple, resident stem/progenitor cell populations that are responsible for the homeostatic maintenance and injury repair of pulmonary epithelium. Though lung epithelial injury in the absence of oncogenic mutation is more commonly expressed as chronic lung disease, lung cancer is the most common form of death worldwide and poses a highly significant risk to human health. Cancer is defined by the cell of origin, responsible for initiating the disease. The Cancer Stem Cell Hypothesis proposes that cancer stem cells, identified by stem-like properties of self-renewal and generation of differentiated progeny, are responsible for propagating growth and spread of the disease. In lung cancer, it is hypothesized that cancer stem cells derive from several possible cell sources. The stem cell-like resistance to injury and proliferative potentials of bronchioalveolar stem cells (BASCs) and alveolar epithelial type II cells (AEC2), as well as cells that express the cancer stem cell marker glycoprotein prominin-1 (CD133) or markers for side populations make them potential reservoirs of lung cancer stem cells. The abnormal activation of pathways that normally regulate embryonic lung development, as well as adult tissue maintenance and injury repair, including the Wnt, Hedgehog (Hh) and Notch pathways, has also been identified in lung tumor cells. It is postulated that therapies for lung cancer that specifically target stem cell signaling pathways utilized by lung cancer stem cells could be beneficial in combating this disease.

Gastric cancer stem cells: A novel therapeutic target

“…Cell surface markers were used because leukemic stem cells can reproduce the tumor after serial xenografting into immunodeficient mice. In recent years, accumulating evidence indicates the presence of CSCs in many solid tumors, including those in brain cancer [65], breast cancer [66], head and neck cancer [67 and references therein], renal cancer [68], colon cancer [69 and references therein], pancreatic cancer [70], liver cancer [71], melanoma [72], and lung cancer [73]. Although many uncertainties have developed in the last few years about the existence of CSCs, recent in vivo evidence suggests that tumors originate from CSCs [74–76].…”

Therapy‐induced enrichment of putative lung cancer stem‐like cells

“…The regulation of CSLCs reveals substantial overlap with normal stem cells, such as the control of pluripotency, stemness, self‐renewal, differentiation and proliferation regulated by the Notch, Wingless (Wnt) and Hedgehog (Hh) pathways . These signalling pathways play vital roles in lung development and may be involved in the regulation of tumourigenesis when mutated, by causing deregulation between self‐renewal and differentiation . The division of stem cells involves the decision of cells to self‐renew or to differentiate.…”

The PLGF/c‐MYC/miR‐19a axis promotes metastasis and stemness in gallbladder cancer

“…Numerous studies have reported that CSCs are responsible for heterogeneity, metastasis, drug resistance, and disease recurrence . Therefore, we also undertook sphere‐formation assays to investigate the effect of PLGF on GBC CSC properties.…”