Expression and function of insulin-like growth factor binding protein 7 (IGFBP-7/ IGFBP-rP1) in glioma cell

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The insulin-like growth factor binding proteins (IGFBPs) are soluble secreted proteins that bind insulin-like growth factor I and II (IGF-I and IGF-II) with affinity that is equal or larger than those of IGF receptors. The IGFBPs are documented to modulate the roles of IGF in regulating cell proliferation and differentiation. IGFBP-7 as a member of IGFBP superfamily, has low affinity to IGF compared with IGFBP-1 to -6, but binds strongly to insulin. IGFBP-7 has been suggested to have tumor suppressive function in breast and prostate cancers. In contrast to the low expression in breast cancer cells, IGFBP-7 was found to be highly expressed in glioma cell lines. The function of IGFBP-7 in glioma tumors is unclear. Using a 35,000 element custom cDNA microarray chip, enriched for glial tumor transcripts, we found that the expression of IGFBP-7 correlated with the grade of glioma tumors. This finding was further validated by real-time RT-PCR and Western blot analysis. We then employed RNAi to examine the role of IGFBP-7 in glioma cells, knocking down IGFBP-7 expression by siRNA transfection. Cell growth analysis showed that cell proliferation was slowed down after IGFBP-7 was knocked down for 5 days. Cell cycle analysis showed that IGFBP-7-depleted cells were arrested at the S-phase. Moreover, glioma cell invasion and migration were attenuated by IGFBP-7 depletion, whereas cell attachment to type IV collagen and vitronectin was enhanced. Western blot analysis showed that expression level of activin, a member of TGF-beta family, was significantly decreased following IGFBP-7 silencing, suggesting that IGFBP-7 mediated regulation of glioma growth, invasion, migration and attachment may be associated with the TGF-β pathway. Taken together, our data suggests that IGFBP-7 may play an important role in glioma growth and tumorigenesis.