EARLY AND EXTENSIVE CONTRIBUTION OF PERICYTES VASCULAR SMOOTH-MUSCLE CELLS TO MICROVASCULAR PROLIFERATION IN GLIOBLASTOMA-MULTIFORME - AN IMMUNO-LIGHT AND IMMUNOELECTRON MICROSCOPIC STUDY/

Although florid microvascular proliferation (MVP) in glioblastoma mult iforme (GEM) has long been considered as proliferation of endothelial cells (EC), recent immuno-light microscopic studies demonstrated many or-smooth muscle actin (alpha-sm actin)-positive cells in this MVP, su ggesting a major contribution of pericytes and/or vascular smooth musc le cells (VSMC). Under certain culture conditions, however, alpha-sm a ctin expression has also been described in EC. In order to further inv estigate to what extent pericytes/VSMC participate in MVP in GEM, we p erformed an immunohistochemical study at both the light and electron m icroscopic levels with anti-alpha-sm actin, with an antibody against E C (EN-4) and with an antibody recently described to react with ''activ ated'; pericytes in conditions with neovascularization (anti-high mole cular weight-melanoma associated antigen). In this detailed study of M VP in GEM, two distinct cell types could be recognized on the basis of a consistent ultrastructural localization and immunophenotype: EC and pericytes/VSMC; no transitional forms were found between these two ce ll types. The contribution of pericytes/VSMC to MVP in GEM was extensi ve and already present in many delicate tumor capillaries, suggesting not only an essential but also an early role of these cells in this ty pe of tumor angiogenesis.