Scatter factor enhances glioma malignancy

Scatter factor (SF) induces angiogenesis and is a mitogen and motility factor for a variety of cell types. Malignant gliomas express SF and its receptor but SF's roles in glioma maligancy are unknown. We examined the effects of SF expression on rat 9L glioma. 9L cells that do not produce SF were transfected with pMEX-SF containing human SF cDNA. SF was detected in conditioned medium (CM) of 9L-SF cells but not in control transfected cells by ELISA and MDCK scatter assay. Proliferation of 9L-SF and control cells were similar but the morphology of 9L-SF lines was more disorganized and less spread. CM from 9L-SF lines stimulated endothelial cell DNA synthesis 2-fold (P < 0.05) and this activity was inhibited by a SF receptor antagonist. Tumor growth in SCID mice following the SQ implantation of 9L-SF cell lines was increased when compared to controls (P<0.01) and some 9L-SF clones formed métastases. Intracranial tumor growth following the implantation to caudate/putamen of all 9L-SF lines tested was also enhanced. Human SF gene expression in vivo was detected by RT-PCR in tumors resulting from the 9L-SF but not control cells. These findings show that SF can increase the malignant phenotype of glial neoplasms in vivo.