[Interstitial lung disease and lung cancer].

Interstitial lung diseases (ILDs) include more than 200 disease entities such as drug induced ILD, radiation pneumonitis, collagen vascular disease-associated interstitial pneumonia, and idiopathic interstitial pneumonias (IIPs). Idiopathic pulmonary fibrosis (IPF) represents the most common IIP, and is one of the most aggressive interstitial lung diseases. ILDs, especially in IPF, are associated with an independent increased risk of lung cancer. Repetitive stimulation, alveolar epithelial injury and dysregulated repair induced by IPF cause genetic errors, which in turn may predispose to the development of lung cancer. We previously established a mouse IgG1 mAb that recognizes a sialylated sugar chain on lung adenocarcinoma cells, designated KL-6. KL-6 is a high-molecular-weight glycoprotein classified as Cluster 9 (MUC1) lung tumor and differentiation antigens. KL-6 has been reported to serve as a sensitive serum marker for interstitial pneumonia and is now clinically used to detect the presence of interstitial pneumonia in Japan; however, recent studies have suggested that it can also be used as a tumor marker as its origin shows. We also found that there is a natural auto-antibody against KL-6 at high levels in sera from healthy volunteers and at low levels in sera from patients with non-small cell lung cancer. The concentration strongly correlated with their good prognoses. Furthermore, we demonstrated that anti-KL-6 mAb induced capping of MUC1 of breast cancer cell lines, which proliferate in suspension culture without aggregation. Moreover, anti-KL-6 mAb enhanced the cytotoxic activity of lymphokine-activated killer cells. The pathogenesis of lung cancer in ILDs is unclear, but some genetic factors seem to be involved. Further studies are needed to clarify the causes and the mechanisms that link ILDs and lung cancer.