The metastasis field welcomes a new member, collapsin response mediator protein-1 (CRMP-1), which is reported to be a lung cancer invasion suppressor gene by Shih et al.(1) in this issue of the Journal. Shih et al. examined differential gene expression among a panel of lung carcinoma cell lines of varying invasive abilities by use of a 9600 complementary DNA microarray analysis. They wisely concentrated on the expression and function of one gene, CRMP-1. The less invasive lung cancer cell lines expressed relatively high levels of CRMP-1 messenger RNA (mRNA) and protein. Transfection of CRMP-1 into the highly invasive CL1–5 cell line reduced invasion through a Matrigel-coated membrane by approximately half. What makes this in vitro cell line observation intriguing is the attendant human lung tumor cohort study. The CRMP-1 mRNA levels of 80 non-small-cell lung carcinoma tumors were determined; patients with high CRMP-1-expressing tumors exhibited statistically significantly longer disease-free and overall survival. Thus, CRMP-1 represents an invasion suppressor with potential relevance to human disease. The data presented are thorough and convincing.

What is CRMP-1? A complex and incompletely understood set of signaling pathways connect CRMP to neural and possibly vascular development and are summarized below. CRMPs can function as inhibitors of axon extension in development, and one can hypothesize a similar signaling network in lung cancer invasion. What is intriguing is that, in development, cells of both the neural and vascular systems invade virtually every tissue. Suppressors of these pathways may, therefore, be of widespread applicability.