Thrombospondin-1 (TSP-1), a well-characterized endogenous inhibitor of angiogenesis, was initially isolated as a constituent of extracellular matrix, and shown to interact with wild-type p53 to regulate angiogenesis (Dameron et al. 1994). More recently, TSP-1 has been shown to modulate mobilization of VEGF directly (Rodriguez-Manzaneque et al. 2001). A number of workers have reported that TSP-1 plays an important role in the differentiation of neurob-lasts induced by retinoic acid treatment (Castle et al. 1992; Pijuan-Thompson et al. 1999). Castle and co-workers reported a rapid induction of TSP-1 when cultured human neuroblastoma cells were treated with retinoic acid (Castle et al. 1992). Furthermore, differentiation was partially prevented by anti-TSP-1 antibody. Because TSP-1 is a negative regulator of VEGF, these findings suggest that differentiation of neuroblasts may be linked to a decrease in proangiogenic signaling. The recent development of TSP-1 mimetic peptides with anti-angio-genic activity is therefore intriguing (Reiher et al. 2002) as such agents may promote neuroblastoma differentiation and inhibit VEGF-stimulated angio-genesis.

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