Yuanyuan Ma

Department of Thoracic Surgery II, Peking UniversityCancer Hospital & Institute

Objective:Tumor initiatingcells (TICs) are a small subpopulation within cancer that is thought to beresistant to conventional therapiesand capable of reinitiating tumors. TICshave similar ability with stem cells including self-renewal, differentiation andto generate the diverse cell types present within a giventumor. However, only afew biomarkers of TICs have been well elucidated. In this report, we haveinvestigated CACNA2D1 to enrich TICs ofnon-small cell lung cancer (NSCLC). Method:Immunofluorescence was used to test CACNA2D1 expression in NSCLC samples.Isolation of CACNA2D1+ and CACNA2D1- subpopulation was carried out fromNSCLC cell lines and tumor specimens by flow cytomery. Phenotypic and functionalcharacterization of stem-like properties was performed in vitro, by assessmentof self-renewal, marker expression, and differentiation, and invivo, bytumorigenicity experiments. The monoclonal antibody against to CACNA2D1 wasgenerated. Result: In comparison to CACNA2D1-, CACNA2D1+ cellsdemonstrated greater TICs properties with higher potential of self-renewal,differentiation and reconstituting tumors. Following treatment, these cellswere enriched inclinical samples. We verified a monoclonal antibody (A2D1-mAb)which targets to CACNA2D1 had therapeutic treatment to TICs of NSCLC andfurther A2D1-mAbcombined with the common anti-cancer drug of carboplatin wasobtained to suppress the established xenograft tumors. Importantly, the diseasefreesurvival and overall survival of NSCLC patients with increased CACNA2D1expression was significantly shorter than that of patients with decreased expression.Conclusion: CACNA2D1 could be used as a marker for identifying TICs ofNSCLC and targeting these cells might provide a way to treat this disease.

KeyWords: Tumorinitiating cells  non-small lungcancer  target