In the present study we described the role of alpha9beta1
integrin in
glioblastoma progression following its interaction with
nerve growth factor (
NGF). The level of expression of alpha9beta1 on
astrocytomas is correlated with increased grade of this
brain tumor and is highest on
glioblastoma, whereas normal astrocytes do not express this
integrin. Two
glioblastoma cell lines, LN229 and LN18, that are alpha9beta1
integrin positive and negative, respectively, were used for alpha9beta1
integrin-dependent
NGF-induced
tumor progression.
NGF was a significant promoter of promigratory and pro-proliferative activities of
glioblastoma cells through direct interaction with alpha9beta1
integrin and activation of MAPK Erk1/2 pathway. The level of
NGF increases approximately threefold in the most
malignant glioma tissue when compared with normal brain. This increase is related to secretion of
NGF by
tumor cells. Specific inhibitors of alpha9beta1
integrin or gene silencing inhibited
NGF-induced proliferation of LN229 cell line to the level shown by LN18 cells. VLO5 promoted alpha9beta1-dependent programmed cell death by induction of intrinsic apoptosis pathway in
cancer cells. LN229 cells were rescued from proapoptotic effect of VLO5 by the presence of
NGF. This
disintegrin significantly inhibited
tumor growth induced by implantation of LN229 cells to the chorioallantoic membrane (CAM) of quail embryonic model, and this inhibitory effect was significantly abolished by the presence of
NGF. alpha9beta1
integrin appears to be an interesting target for blocking the progression of
malignant gliomas, especially in light of the stimulatory effect of
NGF on the development of these
tumors and its ability to transfer proapoptotic signals in
cancer cells.