Fig. 1.

Experimental design and long-term goal of this study. Cancer cell repopulation during courses of chemotherapy and possibly mesothelioma stem cells (MSC) might play critical roles in tumor relapse. a Murine mesothelioma RN5 cells were treated with conventional therapy (cisplatin or γ-ray radiation) and surviving cells were collected for further experiments to evaluate tumorigenicity and gene expression profiles; b RN5 cells were transduced with lentivirus and selected with puromycin resulting in RN5-EOS-P2 cells enriched in MSC. Microarray analysis was performed to screen for gene profiles specific for MSC. c AB12 tumor growth in Balb/c mice after treatment with cisplatin once weekly, 5 μg/kg body weight, up to 4 cycles (Rx1–4) to mimic clinical settings (n = 5 mice). Tumor growth delay was achieved by each cycle of chemotherapy, however, tumors grew back rapidly due to cancer cell repopulation between courses of weekly chemotherapy. NoRx: no treatment, Rx1–4: number of doses of cisplatin; d Modeling the effects of specific MSC targeting: the model is based on the assumption that targeting MSC would delay/prevent tumor repopulation during the intervals of chemotherapy (blue curve) in comparison to conventional treatment (red curve) that mostly targets non-MSC