Pathogenesis of development of lung cancer in idiopathic interstitial pneumonia--growth factors in bronchoalveolar lavage fluid

Abstract

It has been generally accepted that lung fibrosis as in idiopathic interstitial pneumonia (IIP) is frequently associated with the development of lung cancer. This observation implies that the mechanism involved in carcinogenesis and/or enhanced proliferation of cancer cells is common to the fibrosing process. However, there are few studies reported on the pathogenesis of associated lung cancer except for several studies assessed from the point of view of surgical pathology. This study was undertaken to learn whether BAL fluid, which reflects the local milieu of the fibrosing process, enhances the proliferation of human lung cancer cell line Lu-99, Lu-65 and rat lung fibroblasts as assessed by 3H-thymidine incorporation. BAL fluid was obtained from patients with IIP (n = 8) and normal volunteers (n = 8). BAL fluids from patients with IIP enhanced the mean incorporation of 3H-thymidine of Lu-99 up to 3.6 times (p < 0.01) compared to that of normal volunteers. Furthermore, the mean incorporation of Lu-65 was increased up to 1.8 times (p < 0.05) by BAL fluids from patients with IIP. In contrast, BAL fluids from patients caused no significant increase of the mean incorporation of rat lung fibroblasts as compared to normal BAL fluids. The enhancing activities on the growth of cancer cell line Lu-99, Lu-65 were eluted in several fractions by high performance liquid chromatography using Superose 12. These observations indicate that the BAL fluid of IIP patients contains factors enhancing the growth of cancer cells.