RATIONALE: Surfactant protein A (SP-A) is a large multimeric protein found in the airways and alveoli of the lungs. SP-A is a member of the collectin family of proteins, characterized by NH2-terminal collagen-like regions and COOH-terminal lectin domains. Although other surfactant proteins such as SP-B function to reduce surface tension in the lungs, SP-A (as well as SP-D) is known to regulate the pulmonary immune response against the variety of pathogens. On the other hand, it is shown that SP-A can be used as a marker of lung adenocarcinoma, suggesting that SP-A may also play important role in lung cancer progression as well as pulmonary immune response.
METHODS: In this study, a human SP-A gene was introduced into the human lung adenocarcinoma cell line PC14PE6 (PC14PE6/SP-A). In vivo effect of SP-A over-expression on cancer progression was examined in experimental lung metastasis model using NUDE mice. Tumor sections were used for immunohistochemistry to determine the tumor cell death and the host cell recruitment.
RESULTS: PC14PE6/SP-A cells produced significantly fewer lung metastatic colonies and pleural effusion compared to vector transfected cells in vivo. Immunohistochemical analysis showed that the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive tumor cells and macrophage recruitment were increased in the lung metastatic colonies produced by PC14PE6/SP-A cells. Among the recruited macrophages in the tumor, M1 antitumor macrophages were increased, while M2 tumor-promoting macrophages were decreased in the tumor produced by PC14PE6/SP-A cells. Moreover, RT-PCR of metastatic lung tissue revealed that the expression of multiple M1 macrophage markers such as IFN-gamma and TNF-alfa was up-regulated in the tumor produced by PC14PE6/SP-A cells, whereas the expression of M2 macrophage markers was not changed.
CONCLUSION: In addition to its protective effect in infectious diseases, SP-A may also have a protective role in non-infectious lung diseases such as lung cancer through modulating host immune response.