Fig. 3. Cancer stem cells and lung

Fig. 3. Cancer stem cells and lung cancer: Pluripotent drug-resistant CSCs and their role within tumour recurrence post-therapy. Lung cancers, in common with many solidtumours and other malignancies have been observed to harbour a small sub-population of cells within the primary tumours that have the ability to self-renew and generatetumours within NOD-SCID mice. Various biomarker proteins have been utilised to enrich these cell sub-populations including: CD133 (prominin), the multi-drug-resistancetransporter protein ABCG2 (Hoechst 33342 dye-effluxing side-population-SP-cells), high-level expression of aldehyde-dehydrogenase isoforms ALDH1A1/ALDH3A1 and thecell surface glycoprotein marker CD44. Immunohistochemical studies of lung tumours and cell-imaging have demonstrated enrichment for these cell-sub-populations duringradio- and chemotherapy of lung cancer, suggesting that they have increased ability to resist the adverse effects of cancer treatment. This may be partially explained by theirexpression of the multi-drug transport protein ABCG2. The cancer stem cell theory proposes that these putative lung cancer CSCs survive treatment and can then differentiateinto the multiple cell-types present within the primary tumour (via their pluripotent and self-renewing phenotype) thus seeding tumour recurrence and eventual diseaserelapse. Analysis of the signalling pathways within these CSC sub-populations has revealed the increased signalling of pathways involved in embryonic cell development andstem cell maintenance in other tissues including the canonical Wnt/b-catenin pathway, as well as Notch-receptor signalling and increased activation of the Hedgehogsignallingpathway.