Inhibition of tumor progression during allergic airway inflammation in a murine model: significant role of TGF-β

TGF-beta is an important mediator of pulmonary allergic inflammation, and it has been recently reported to be a potential inhibitor of lung tumor progression. The correlation between cancer and allergic inflammatory diseases remains controversial. Thus, the aim of the present study was to evaluate the effects of pulmonary allergic inflammation and in particular the role of TGF-beta on cancer progression. Cancer cells were implanted in a BALB/c mice model of allergic airway inflammation, and tumor growth was measured. Apoptosis was evaluated by TUNEL assay, and TGF-beta was measured by ELISA. Expression of proliferating cell nuclear antigen, TGF-beta, TGF-beta receptors I and II, phospho-Smad2 and phospho-Smad4 was evaluated by immunohistochemistry and quantified using digital pathology. The effect of a TGF-beta activity inhibitor and recombinant TGF-beta on tumor growth was analyzed. The effect of exogenous TGF-beta on cell proliferation and apoptosis was evaluated in vitro. Mice with allergic airway inflammation exhibited decreased tumor volumes due to cell proliferation inhibition and increased apoptosis. TGF-beta was increased in the sera and tumor tissues of allergic mice. TGF-beta activity inhibition increased tumor progression in allergic mice by enhancing proliferation and decreasing apoptosis of tumor cells. The administration of TGF-beta resulted in reduced tumor growth. This study is the first to establish an inverse relationship between allergic airway inflammation and tumor progression. This effect appears to be mediated by TGF-beta, which is overexpressed in tumor cells during pulmonary allergic inflammation. This study indicates that TGF-beta is a potential target for antitumor therapy.