Neuroendocrine cells along the digestive tract express neuropilin-2

Neuropilin-2 (np-2) is a receptor for semaphorin-3F (sema-3F) and semaphori n-3C (sema-3C). These semaphorins repel tips of growing axons that express np-2. In addition, np-2 functions as a receptor for heparin binding forms o f the angiogenic factor vascular endothelial growth factor (VEGF) such as V EGF(145) and VEGF(165). We report that np-2 is strongly expressed in neuroe ndocrine cells located all along the human digestive tract. Confocal fluore scent microscopy revealed that np-2 is concentrated in vesicle-like structu res located near the nucleus at the basolateral side of these cells. In the colon, the np-2-expressing subpopulation of neuroendocrine cell is almost identical with the serotonin-producing subpopulation of neuroendocrine cell s. Gastrointestinal carcinoid tumors are digestive tract tumors that develo p from neuroendocrine cells. Interestingly, most of the carcinoid tumors de rived from the colon and the appendix did not contain np-a-producing cells. However, some carcinoid tumors derived from the small intestine and stomac h did express low levels of np-2 in isolated foci of cells. By contrast, st rong serotonin and chromogranin-A expression was observed in all of the car cinoid tumors that were examined. These results suggest that loss of np-2 e xpression may accompany tumor progression in carcinoid tumors. (C) 2001 Aca demic Press.