Locally ablative radio therapy of a primary human small cell lung cancer tumor decreases the number of spontaneous metastases in two xenograft models
Menée à l'aide de deux xénogreffes de cancer du poumon non à petites cellules sur des modèles murins, cette étude montre qu'une radiothérapie localisée ablative inhibe le développement de métastases
Introduction : Cancer patients mainly die from distant metastases, for which small cell lung cancer (SCLC) serves as an instructive example. As it is still under debate whether radiation therapy (RT), surgery (OP), radio-chemotherapy (RChT) or chemotherapy (ChT) may promote metastatic spread, we investigated the influence of these treatments on SCLC metastases in two xenograft models. Methods and materials : 1 x 106 human SCLC cells (OH1, H69) were subcutaneously injected into SCID mice to form a local primary tumor node at the lower trunk. RT, OP, RChT, or ChT were started after development of palpable tumors. ChT was given as a single intraperitoneal injection of cisplatin. RT was 5 x 10 Gy on the local tumor node. Two additional groups were implemented to assess primary tumors and distant metastases in untreated mice at the beginning (control groups A) and at the end of the experiment (control groups B). Pro-apoptotic, anti-proliferative, anti-angiogenic, and hypoxic effects were assessed by Feulgen, Ki-67, S1P1 receptor, and HIF1
α staining, respectively. Quantitative Alu-PCR was used to determine circulating tumor cells (CTCs) in the blood, and disseminated tumor cells (DTCs) in the lungs, bone marrow, liver, and brain. Results
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In both xenograft models, RT and RChT abrogated local tumor growth indicated by increased apoptosis, decreased cell proliferation, and reduced microvessel density (equally affecting vessels of all diameters). Regarding metastases, RT and RChT not only counteracted the time-dependent increase of dissemination, but also decreased the metastatic load pre-existing at therapy induction in the blood, lungs, and liver. Only in case of relapse-free surgery, similar effects could be achieved by OP. Conclusion
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Our models provide evidence that RT and RChT ablate the primary tumor and inhibit metastasis development over time. Upon local recurrence, RT showed beneficial effects compared with OP with regards to suppression of CTCs and DTCs.