Stromal angiogenesis in human glioma: a role of platelet-derived endothelial cell growth factor

Although several tumor angiogenic factors have been identified previously and characterized, it is not yet fully clear how tumor angiogenic factors induce endothelial cell transformation and proliferation. Platelet-derived endothelial cell growth factor (PD-ECGF) has been recently discovered to be an endothelial cell growth factor initially purified from human platelets. However, there has been no previous report describing the significance of PD-ECGF in the growth of brain tumors by angiogenic stimulation. We report the immunohistochemical localization of PD-ECGF in human gliomas and meningiomas, and discuss whether PD-ECGF could play a role in the modulation of stromal angiogenesis in human glioblastoma multiforme.

Twenty-eight cases of glioma (11 glioblastomas and 17 astrocytomas) derived from the neuroectoderm in embryogenesis and 12 meningiomas from the mesoderm were investigated by both immunohistochemical localization of the PD-ECGF and a semiquantitative assay to determine the degree of stromal angiogenesis.

Numerous PD-ECGF positive cells were observed within and around the blood vessels of glioblastoma multiforme, especially on the borders of tumor tissue. The PD-ECGF positive cells were negative for anti-von Willebrand factor (vWF) and antiglial fibrillary acidic protein (GFAP) antibodies and were positive for antimacrophage (HAM-56). The expression of PD-ECGF by macrophages closely correlated with the degree of stromal vascularity in glioblastoma multiforme; no such correlation was found in either astrocytoma or meningioma. Proliferating cell nuclear antigen (PCNA) was found to be positive in some endothelial cells of stromal vessels in glioblastoma multiforme. These findings suggest that PD-ECGF expressed by macrophages plays an important role in the growth of glioblastoma multiforme with stromal angiogenesis.