title: The expression of vascular endothelial platelet endothelial cell adhesion molecule-1 is not regulated by IFN-gamma treatment of C6 tumors in vivo.
abstract: Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a glycoprotein that is constitutively expressed on the surface of endothelial cells, leukocytes, platelets, monocytes and neutrophils. It has been proposed that PECAM-1 plays a role in transendothelial leukocyte trafficking. In vitro studies have suggested that interferon-gamma (IFN-gamma) may regulate PECAM-1 expression on endothelial cells. We have investigated the in vivo regulatory role of mouse IFN-gamma (mIFN-gamma) on the expression of PECAM-1 on vascular endothelial cells during tumor angiogenesis. In situ retroviral gene transfer was used to deliver mIFN-gamma into established subcutaneous tumors in athymic (nu/nu) mice. The biological activity of mIFN-gamma expressed intratumorally, was verified by i) a macrophage and granulocyte (predominantly neutrophil) infiltrate observed within C6 tumors following mIFN-gamma treatment; ii) an up-regulation of major histocompatibility complex (MHC) class I and II expression on the surface of tumor cells following mIFN-gamma treatment. Indirect immunohistochemical localisation of PECAM-1 expression was performed on control and mIFN-gamma-treated C6 tumor sections. The intensity and distribution of PECAM-1 expression on vascular endothelial cells in mIFN-gamma-treated tumors was similar to control tumors. Immunohistochemical staining of PECAM-1 was compared to factor VIII-related antigen in serial tumor sections. No differences were observed between the vascular endothelial cells expressing PECAM-1 and factor VIII in serial sections of control and mIFN-gamma-treated tumors. Therefore, in this in vivo C6 tumor model, IFN-gamma does not alter PECAM-1 expression on tumor-associated vascular endothelial cells.
authors.affiliation: Gene Therapy Laboratory, The Department of Surgery, The University of Melbourne and The Royal Melbourne Hospital, Parkville Victoria 3052, Australia.
authors.forename: N K
authors.initials: NK
authors.lastname: Jonas
authors.forename: M
authors.initials: M
authors.lastname: Saleh
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D015316:Genetic Therapy; D005910:Glioma / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D006801:Humans; D007249:Inflammation; D007371:Interferon-gamma / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000503:physiopathology* / Q000628:therapy; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D014841:von Willebrand Factor / Q000096:biosynthesis / Q000235:genetics
chemical_list: D009363:Neoplasm Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011993:Recombinant Fusion Proteins; D014841:von Willebrand Factor; D007371:Interferon-gamma