Cell-retained isoforms of vascular endothelial growth factor (VEGF) are correlated with poor prognosis in osteosarcoma |
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| Affiliation: | 1. Department of PathologyJapan;2. Department of Orthopaedics, Tokai University School of Medicine, Bohseidai, Isehara-shi, Kanagawa 259-1193Japan;3. Department of Orthopaedic Surgery, Teikyo University School of Medicine, Tokyo, Japan;1. Center for Innovation to Implementation, VA Palo Alto Health Care System, Menlo Park, CA, USA;2. Division of Primary Care & Population Health, Stanford University, Stanford, CA, USA;3. Stanford University, School of Medicine, Stanford University, Stanford, CA, USA;1. Assistant Professor, Department of Stomatology, University of Granada, Granada, Spain;2. Assistant Professor, Department of Nursing, Faculty of Health Sciences, University of Granada, Granada, Spain;3. Assistant Professor, Department of Nursing, Faculty of Health Sciences, University of Granada, Granada, Spain;4. Associate Professor, Professor, Department of Stomatology, University of Granada, Granada, Spain;6. Associate Professor, Department of Nursing, Faculty of Health Sciences, University of Granada, Granada, Spain;5. Professor, Department of Nursing, Faculty of Health Sciences, University of Granada, Granada, Spain;1. Department of Orthopaedics, Xuhui Central Hospital, Shanghai, 200031, China;2. Department of Joint Center, Changzheng Hospital, the Second Military Medical University, No. 440, North Chengdu Road, Shanghai, 200003, China;1. Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia;2. Institute of Oncology Ljubljana, Zaloška 2, 1000 Ljubljana, Slovenia;3. Oncology and Haematology Unit, University Children''s Hospital, University Medical Centre, Bohoričeva 20, 1000 Ljubljana, Slovenia |
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| Abstract: | ![]()
Vascular endothelial growth factor (VEGF) is a major angiogenic factor. Osteosarcoma is characterised by hypervascularity and metastatic potential. We examined VEGF mRNA expression, VEGF isoform pattern and VEGF receptor (flt-1 and KDR) by RT-PCR analysis in 30 osteosarcomas. All 30 osteosarcomas expressed VEGF mRNA. 17 osteosarcomas (57%) expressed flt-1 mRNA, whilst 20 (67%) expressed KDR mRNA. 6/30 (20%) osteosarcomas were positive for VEGF121 only, 8 (27%) for VEGF121+VEGF165, and 16 (53%) for VEGF121+VEGF165+VEGF189. Patients with osteosarcomas with VEGF165 (n=24) had significantly poorer prognosis in comparison with those without VEGF165 (P=0.022, Wilcoxon's test). The osteosarcomas with VEGF165 had significantly increased vascularity assessed on sections immunostained for CD34 (P<0.001, Mann–Whitney U test). Although VEGF165 is a soluble isoform, it is also retained on the cellular surface. These results suggest that cell-retained VEGF isoforms (VEGF165, VEGF189) might be essential for neovascularisation in osteosarcoma, whilst the soluble VEGF121 isoform is not sufficient to stimulate neovascularisation in this type of neoplasm. |
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