GROWTH-FACTOR AND PEPTIDE RECEPTORS IN SMALL-CELL LUNG-CANCER

In the past decade, over 1000 continuous human cell lines have been established from lung cancer biopsy specimens. Numerous growth factors and receptors have been identified in the small cell lung cancer (SCLC) cell lines. SCLC is a neuroendocrine tumor which contains numerous peptides, including bombesin/gastrin releasing peptide (BN/GRP), and receptors. High levels of GRP mRNA and immunoreactivity are present in SCLC cells. The secretion rate of GRP from SCLC cells is increased by vasoactive intestinal peptide (VIP), which elevates the intracellular cAMP. GRP binds to cell surface receptors, elevates cytosolic calcium and stimulates the growth of SCLC cells. Additional SCLG growth factors include insulin-like growth factor I (IGF-I) and transferrin. IGF-I mRNA and protein is present in SCLC. IGF-I binds with high affinity to SCLC cells and stimulates tyrosine kinase activity and growth. Transferrin is also present in SCLC cells. Transferrin binds with high affinity to SCLC cells and stimulates iron transport and growth. Synthetic peptide antagonists and monoclonal antibodies have been identified which disrupt autocrine growth pathways and inhibit SCLC growth.