Over 90,000 males and 40,000 females in the United States develop lung cancer annually. The four main types of lung cancer are small cell lung cancer (SCLC), a neuroendocrine tumor which responds to chemo- and/or radiation therapy, adenocarcinoma, large cell carcinoma and squamous cell carcinoma. We found that SCLC produces bombesin-like peptides, which function as autocrine growth factors. Little is known about the biochemical properties of non-small cell lung cancer (NSCLC). Recently, we observed that vasoactive intestinal polypeptide (VIP) binds with high affinity to NSCLC cell lines as well as SCLC. These data suggest that VIP receptors may represent a common cell surface antigen on all types of lung cancer. In addition, epidermal growth facto (EGF) receptors are present in high density on adenocarcinoma, large cell carcinoma and squamous cell carcinoma cells but are present only in low density on SCLC cells. This proposal concerns the biological role of VIP and EGF receptors in NSCLC.
The specific aims are to: 1) determine the binding and second messenger properties of adenocarcinoma, large cell carcinoma and squamous cell carcinoma cell lines. Also, the ability of VIP and EGF to bind to biopsy specimens will be determined using in vitro autoradiographic techniques. These studies will elucidate if neuropeptide and growth factor receptors are present in tumors as well as the subsequently derived cell lines. 2) The VIP receptor from NSCLC cells will be characterized biochemically using crosslinking techniques. Also, the VIP receptor will be solubilized and purified in order learn more about the molecular structure of VIP receptors. 3) Monoclonal antibodies will be developed against the human VIP receptor. These antibodies may serve as unique probes for the VIP receptor. 4) The ability of VIP receptor agonists and antagonists as well as monoclonal antibodies against the EGF receptor to alter the growth of NSCLC will be determined. A hypothesis to be tested is that neuropeptide and growth factor receptors regulate the growth of NSCLC. The long term objective of this study is to investigate the role neuropeptides and growth factor receptors in lung cancer. These studies will further define the cell surface receptors present on lung cancer cells and aid in determining if these receptors can be utilized to develop novel therapeutic approaches for the treatment of lung cancer.
