title: Angiogenic growth factor expression in benign and malignant vascular tumours.
abstract: Angiosarcomas are rare malignant vascular tumours. Angiosarcoma expression of vascular endothelial growth factor (VEGF) has previously been reported, but angiosarcoma expression of other angiogenic growth factors has not been systematically studied. Non-VEGF angiogenic growth factors are a potential mechanism of resistance to VEGF-targeted therapy, but they also represent potential therapeutic targets. Immunohistochemistry analysis evaluated the expression of 13 angiogenic growth factors and receptors in 27 separate benign and malignant archived human vascular tumour samples. The expression of 55 angiogenesis-related proteins was subsequently profiled in five fresh human angiosarcoma tumour samples using antibody arrays. Angiosarcomas expressed a variety of angiogenic growth factors. Significantly higher levels of Notch1 were detected compared with benign haemangiomas (p=0.033), but lower levels of basic fibroblast growth factor (bFGF) compared to benign haemangiomas (p=0.07) and inflammatory vascular lesions (p=0.009). Vascular tumour expression of FGF receptor (FGFR)-1 correlated with angiopoietin (Ang)-2, Tie2, hepatocyte growth factor (HGF) and Notch1 expression (p=0.001, p=0.001, p<0.001 and p<0.001 respectively). Notch1 also correlated with Tie2 expression (p=0.004). In conclusion, angiosarcomas express multiple angiogenic growth factors. Treatments could be targeted at individual angiogenic growth factors. However, our findings provide a rationale for combination therapy, or for treatments that target common downstream signalling intermediaries, such as Akt, mTOR or ERK.
authors.affiliation: Academic Unit of Clinical Oncology, Weston Park Hospital, Whitham Rd, Sheffield S10 2SJ, UK; Academic Unit of Surgical Oncology, Medical School, Beech Hill Rd, University of Sheffield, Sheffield S10 2RX, UK. Electronic address: r.j.young@sheffield.ac.uk.
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Young
authors.affiliation: Department of Histopathology, Sheffield Teaching Hospitals NHS Foundation Trust, Glossop Rd, Sheffield S10 2JF, UK. Electronic address: malee.fernando@sth.nhs.uk.
authors.forename: Malee
authors.initials: M
authors.lastname: Fernando
authors.affiliation: Department of Histopathology, Sheffield Teaching Hospitals NHS Foundation Trust, Glossop Rd, Sheffield S10 2JF, UK. Electronic address: david.hughes@sth.nhs.uk.
authors.forename: David
authors.initials: D
authors.lastname: Hughes
authors.affiliation: Academic Unit of Surgical Oncology, Medical School, Beech Hill Rd, University of Sheffield, Sheffield S10 2RX, UK. Electronic address: n.j.brown@sheffield.ac.uk.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Brown
authors.affiliation: Academic Unit of Clinical Oncology, Weston Park Hospital, Whitham Rd, Sheffield S10 2SJ, UK. Electronic address: p.j.woll@sheffield.ac.uk.
authors.forename: Penella J
authors.initials: PJ
authors.lastname: Woll
mesh_terms: D042501:Angiogenic Proteins / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D017789:Granuloma, Pyogenic / Q000378:metabolism / Q000473:pathology; D006391:Hemangioma / Q000378:metabolism* / Q000473:pathology; D006394:Hemangiosarcoma / Q000378:metabolism* / Q000473:pathology; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism; D051881:Receptor, Notch1 / Q000378:metabolism; D042787:Receptor, TIE-2 / Q000378:metabolism; D012983:Soft Tissue Neoplasms; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042501:Angiogenic Proteins; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D017228:Hepatocyte Growth Factor; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D042787:Receptor, TIE-2
keywords: Angiogenesis; Angiosarcoma; VEGF