| Lung cancer has been one of the most severe threats to humans with the highest mortality rate in the world. Eight-five percent of its incidences are associated with non-small-cell lung cancer(NSCLC). Although cancer stem cells(CSCs) are suggested to be responsible for tumor initiation, metastasis, relapse and therapeutic resistance, few CSC markers have been identified and/or validated functionally to enrich the malignant population in human lung tumors. Here, we report two novel CSC markers CD49 f and CD104 for human NSCLC. Sphere-forming CSCs are enriched in the CD49 fhi, CD104- or the previously reported CD166+ compartment. A novel CD166+CD49fhiCD104-Lin- population with a mean frequency of 1.4±0.4% is readily isolated in human NSCLC specimens regardless of histological subtypes and genetic driver mutations. This population is tumorigenic and capable of self-renewing, as it is able to robustly develop tumor spheres in vitro and reconstitute orthotopic lung tumors in immune-compromised mice in vivo through serial passages. Consistently, the isolated lung CSCs(LCSCs) show a higher expression of stemness genes(e.g.GLDC, LIN28 B, ALDH1, and TGFβ1), characteristics of partial epithelial-mesenchymal transition(EMT) and strong resistance to cisplatin treatment. Taken together, our data indicate that the novel CD166+CD49fhiCD104-Lin- cells are significantly enriched for LCSCs and are important for a better understanding of tumorigenesis in lung cancer. |
