Abstract
Local recurrence of lung cancer following radiofrequency ablation (RFA) treatment is common. The aims of the present study were to assess how RFA treatment affects the growth of small cell lung cancer (SCLC) micrometastases in the transition zone (TZ) surrounding the ablated region and in the reference zones (RZs) of the ablated or unablated lobes and to identify the molecular mechanism(s) of lung cancer recurrence following RFA treatment. After lung micrometastases of human SCLCs had formed, RFA treatment was applied to the right upper lobe (RUL) of the lung in nude mice. Hypoxia inducible factor (HIF)-1α expression, proliferation and angiogenesis potential both in the TZ and RZ were evaluated over time. Separately, at day 1, 7 and 14 following RFA treatment, the growth of micrometastases showed an ~2-fold increase in the TZ compared to the RZ of the unablated lobe, as the right lower lobe (RLL) and the growth of micrometastases in the RZ of the RUL was also induced by RFA. In addition, accelerated tumor growth in the TZ was induced by HIF-1α, but was not associated with tissue angiogenesis potential. We concluded that local recurrences of SCLCs caused by overproliferation of micrometastases following RFA treatment were driven by HIF-1α, although angiogenesis was not the driving force in the TZ.