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Erschienen in: International Orthopaedics 11/2012

01.11.2012 | Original Paper

Expression of Vascular Endothelial Growth Factor correlates with the advance of clinical osteosarcoma

verfasst von: John Lammli, Minyan Fan, Howard G. Rosenthal, Meghan Patni, Elizabeth Rinehart, Gerardo Vergara, Elizabeth Ablah, Paul H. Wooley, George Lucas, Shang-You Yang

Erschienen in: International Orthopaedics | Ausgabe 11/2012

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Abstract

Purpose

Osteosarcoma is the most common primary malignancy in orthopaedic surgery. Studies suggest that expression of VEGF and high vascularity within osteosarcoma may correlate with poor prognosis. The purpose of this study was to determine whether there was a correlation of VEGF expression with clinical tumour stage and metastasis.

Methods

This retrospective case series examined 54 cases of osteosarcoma patients who were treated during a ten-year period. Relevant clinical information included age, gender, tumour location, stage, adjuvant therapy, morbidity, mortality, and tumour subtypes. The clinical information was analysed for correlation of VEGF expression and tumour prognosis. Tumour sections were examined by routine H&E and by immunohistochemistry for VEGF, CD31, and the oncogenes c-myc and c-fos.

Results

There was a significantly positive correlation between VEGF expression and tumour stages among these cases (p < 0.01). The data also suggested a higher cancer recurrence and more frequent cases of remote metastasis in the high-VEGF group compared to the low-VEGF group. VEGF expression also positively associated with c-fos and c-myc expressions in the primary tumour sections.

Conclusion

The results of this study highlight the role of VEGF in angiogenesis and tumour burden. Data also suggest the influence of VEGF may associate with the elevations of c-fos and c-myc expression. The development of novel therapies to target the VEGF pathway in osteosarcoma may lead to improved survival.
Literatur
1.
Zurück zum Zitat Messerschmitt PJ, Garcia RM, Abdul-Karim FW, Greenfield EM, Getty PJ (2009) Osteosarcoma. J Am Acad Orthop Surg 17(8):515–527PubMed Messerschmitt PJ, Garcia RM, Abdul-Karim FW, Greenfield EM, Getty PJ (2009) Osteosarcoma. J Am Acad Orthop Surg 17(8):515–527PubMed
2.
Zurück zum Zitat Rosen G, Suwansirikul S, Kwon C, Tan C, Wu SJ, Beattie EJ Jr, Murphy ML (1974) High-dose methotrexate with citrovorum factor rescue and adriamycin in childhood osteogenic sarcoma. Cancer 33(4):1151–1163PubMedCrossRef Rosen G, Suwansirikul S, Kwon C, Tan C, Wu SJ, Beattie EJ Jr, Murphy ML (1974) High-dose methotrexate with citrovorum factor rescue and adriamycin in childhood osteogenic sarcoma. Cancer 33(4):1151–1163PubMedCrossRef
3.
Zurück zum Zitat Coomber BL, Denton J, Sylvestre A, Kruth S (1998) Blood vessel density in canine osteosarcomas. Can J Vet Res 62(3):199–204PubMed Coomber BL, Denton J, Sylvestre A, Kruth S (1998) Blood vessel density in canine osteosarcomas. Can J Vet Res 62(3):199–204PubMed
4.
Zurück zum Zitat Keck PJ, Hauser SD, Krivi G, Sanzo K, Warren T, Feder J, Connolly DT (1989) Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science 246(4935):1309–1312PubMedCrossRef Keck PJ, Hauser SD, Krivi G, Sanzo K, Warren T, Feder J, Connolly DT (1989) Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science 246(4935):1309–1312PubMedCrossRef
5.
Zurück zum Zitat Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246(4935):1306–1309PubMedCrossRef Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246(4935):1306–1309PubMedCrossRef
6.
Zurück zum Zitat Sallinen H, Anttila M, Narvainen J, Koponen J, Hamalainen K, Kholova I, Heikura T, Toivanen P, Kosma VM, Heinonen S, Alitalo K, Yla-Herttuala S (2009) Antiangiogenic gene therapy with soluble VEGFR-1, -2, and -3 reduces the growth of solid human ovarian carcinoma in mice. Mol Ther 17(2):278–284. doi:10.1038/mt.2008.258 PubMedCrossRef Sallinen H, Anttila M, Narvainen J, Koponen J, Hamalainen K, Kholova I, Heikura T, Toivanen P, Kosma VM, Heinonen S, Alitalo K, Yla-Herttuala S (2009) Antiangiogenic gene therapy with soluble VEGFR-1, -2, and -3 reduces the growth of solid human ovarian carcinoma in mice. Mol Ther 17(2):278–284. doi:10.​1038/​mt.​2008.​258 PubMedCrossRef
7.
Zurück zum Zitat Jia ZZ, Jiang GM, Feng YL (2011) Serum HIF-1alpha and VEGF levels pre- and post-TACE in patients with primary liver cancer. Chin Med Sci J (Chung-kuo i hsueh k'o hsueh tsa chih/Chinese Academy of Medical Sciences) 26(3):158–162 Jia ZZ, Jiang GM, Feng YL (2011) Serum HIF-1alpha and VEGF levels pre- and post-TACE in patients with primary liver cancer. Chin Med Sci J (Chung-kuo i hsueh k'o hsueh tsa chih/Chinese Academy of Medical Sciences) 26(3):158–162
8.
Zurück zum Zitat Roland CL, Dineen SP, Lynn KD, Sullivan LA, Dellinger MT, Sadegh L, Sullivan JP, Shames DS, Brekken RA (2009) Inhibition of vascular endothelial growth factor reduces angiogenesis and modulates immune cell infiltration of orthotopic breast cancer xenografts. Mol Cancer Ther 8(7):1761–1771. doi:10.1158/1535-7163.MCT-09-0280 PubMedCrossRef Roland CL, Dineen SP, Lynn KD, Sullivan LA, Dellinger MT, Sadegh L, Sullivan JP, Shames DS, Brekken RA (2009) Inhibition of vascular endothelial growth factor reduces angiogenesis and modulates immune cell infiltration of orthotopic breast cancer xenografts. Mol Cancer Ther 8(7):1761–1771. doi:10.​1158/​1535-7163.​MCT-09-0280 PubMedCrossRef
9.
Zurück zum Zitat Tokunaga T, Oshika Y, Abe Y, Ozeki Y, Sadahiro S, Kijima H, Tsuchida T, Yamazaki H, Ueyama Y, Tamaoki N, Nakamura M (1998) Vascular endothelial growth factor (VEGF) mRNA isoform expression pattern is correlated with liver metastasis and poor prognosis in colon cancer. Br J Cancer 77(6):998–1002PubMedCrossRef Tokunaga T, Oshika Y, Abe Y, Ozeki Y, Sadahiro S, Kijima H, Tsuchida T, Yamazaki H, Ueyama Y, Tamaoki N, Nakamura M (1998) Vascular endothelial growth factor (VEGF) mRNA isoform expression pattern is correlated with liver metastasis and poor prognosis in colon cancer. Br J Cancer 77(6):998–1002PubMedCrossRef
10.
Zurück zum Zitat Yuan A, Yu CJ, Kuo SH, Chen WJ, Lin FY, Luh KT, Yang PC, Lee YC (2001) Vascular endothelial growth factor 189 mRNA isoform expression specifically correlates with tumor angiogenesis, patient survival, and postoperative relapse in non-small-cell lung cancer. J Clin Oncol 19(2):432–441PubMed Yuan A, Yu CJ, Kuo SH, Chen WJ, Lin FY, Luh KT, Yang PC, Lee YC (2001) Vascular endothelial growth factor 189 mRNA isoform expression specifically correlates with tumor angiogenesis, patient survival, and postoperative relapse in non-small-cell lung cancer. J Clin Oncol 19(2):432–441PubMed
11.
Zurück zum Zitat Lee YH, Tokunaga T, Oshika Y, Suto R, Yanagisawa K, Tomisawa M, Fukuda H, Nakano H, Abe S, Tateishi A, Kijima H, Yamazaki H, Tamaoki N, Ueyama Y, Nakamura M (1999) Cell-retained isoforms of vascular endothelial growth factor (VEGF) are correlated with poor prognosis in osteosarcoma. Eur J Cancer 35(7):1089–1093PubMedCrossRef Lee YH, Tokunaga T, Oshika Y, Suto R, Yanagisawa K, Tomisawa M, Fukuda H, Nakano H, Abe S, Tateishi A, Kijima H, Yamazaki H, Tamaoki N, Ueyama Y, Nakamura M (1999) Cell-retained isoforms of vascular endothelial growth factor (VEGF) are correlated with poor prognosis in osteosarcoma. Eur J Cancer 35(7):1089–1093PubMedCrossRef
12.
Zurück zum Zitat Kaya M, Wada T, Akatsuka T, Kawaguchi S, Nagoya S, Shindoh M, Higashino F, Mezawa F, Okada F, Ishii S (2000) Vascular endothelial growth factor expression in untreated osteosarcoma is predictive of pulmonary metastasis and poor prognosis. Clin Cancer Res 6(2):572–577PubMed Kaya M, Wada T, Akatsuka T, Kawaguchi S, Nagoya S, Shindoh M, Higashino F, Mezawa F, Okada F, Ishii S (2000) Vascular endothelial growth factor expression in untreated osteosarcoma is predictive of pulmonary metastasis and poor prognosis. Clin Cancer Res 6(2):572–577PubMed
13.
Zurück zum Zitat Ben Josef E, Yang SY, Ji TH, Bidart JM, Garde SV, Chopra DP, Porter AT, Tang DG (1999) Hormone-refractory prostate cancer cells express functional follicle-stimulating hormone receptor (FSHR). J Urol 161(3):970–976PubMedCrossRef Ben Josef E, Yang SY, Ji TH, Bidart JM, Garde SV, Chopra DP, Porter AT, Tang DG (1999) Hormone-refractory prostate cancer cells express functional follicle-stimulating hormone receptor (FSHR). J Urol 161(3):970–976PubMedCrossRef
14.
Zurück zum Zitat Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1(1):27–31PubMedCrossRef Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1(1):27–31PubMedCrossRef
15.
Zurück zum Zitat Weidner N, Carroll PR, Flax J, Blumenfeld W, Folkman J (1993) Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am J Pathol 143(2):401–409PubMed Weidner N, Carroll PR, Flax J, Blumenfeld W, Folkman J (1993) Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am J Pathol 143(2):401–409PubMed
16.
Zurück zum Zitat Weidner N, Folkman J (1996) Tumoral vascularity as a prognostic factor in cancer. Important Adv Oncol 167–190 Weidner N, Folkman J (1996) Tumoral vascularity as a prognostic factor in cancer. Important Adv Oncol 167–190
17.
Zurück zum Zitat Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86(3):353–364PubMedCrossRef Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86(3):353–364PubMedCrossRef
18.
19.
Zurück zum Zitat Folkman J (2002) Role of angiogenesis in tumor growth and metastasis. Semin Oncol 29(6 Suppl 16):15–18PubMed Folkman J (2002) Role of angiogenesis in tumor growth and metastasis. Semin Oncol 29(6 Suppl 16):15–18PubMed
20.
Zurück zum Zitat Suzuki K, Hayashi N, Miyamoto Y, Yamamoto M, Ohkawa K, Ito Y, Sasaki Y, Yamaguchi Y, Nakase H, Noda K, Enomoto N, Arai K, Yamada Y, Yoshihara H, Tujimura T, Kawano K, Yoshikawa K, Kamada T (1996) Expression of vascular permeability factor/vascular endothelial growth factor in human hepatocellular carcinoma. Cancer Res 56(13):3004–3009PubMed Suzuki K, Hayashi N, Miyamoto Y, Yamamoto M, Ohkawa K, Ito Y, Sasaki Y, Yamaguchi Y, Nakase H, Noda K, Enomoto N, Arai K, Yamada Y, Yoshihara H, Tujimura T, Kawano K, Yoshikawa K, Kamada T (1996) Expression of vascular permeability factor/vascular endothelial growth factor in human hepatocellular carcinoma. Cancer Res 56(13):3004–3009PubMed
21.
Zurück zum Zitat Cole MD, McMahon SB (1999) The Myc oncoprotein: a critical evaluation of transactivation and target gene regulation. Oncogene 18(19):2916–2924PubMedCrossRef Cole MD, McMahon SB (1999) The Myc oncoprotein: a critical evaluation of transactivation and target gene regulation. Oncogene 18(19):2916–2924PubMedCrossRef
22.
Zurück zum Zitat van den Berg S, Rahmsdorf HJ, Herrlich P, Kaina B (1993) Overexpression of c-fos increases recombination frequency in human osteosarcoma cells. Carcinogenesis 14(5):925–928PubMedCrossRef van den Berg S, Rahmsdorf HJ, Herrlich P, Kaina B (1993) Overexpression of c-fos increases recombination frequency in human osteosarcoma cells. Carcinogenesis 14(5):925–928PubMedCrossRef
23.
Zurück zum Zitat Wu JX, Carpenter PM, Gresens C, Keh R, Niman H, Morris JW, Mercola D (1990) The proto-oncogene c-fos is over-expressed in the majority of human osteosarcomas. Oncogene 5(7):989–1000PubMed Wu JX, Carpenter PM, Gresens C, Keh R, Niman H, Morris JW, Mercola D (1990) The proto-oncogene c-fos is over-expressed in the majority of human osteosarcomas. Oncogene 5(7):989–1000PubMed
24.
Zurück zum Zitat Gamberi G, Benassi MS, Bohling T, Ragazzini P, Molendini L, Sollazzo MR, Pompetti F, Merli M, Magagnoli G, Balladelli A, Picci P (1998) C-myc and c-fos in human osteosarcoma: prognostic value of mRNA and protein expression. Oncology 55(6):556–563PubMedCrossRef Gamberi G, Benassi MS, Bohling T, Ragazzini P, Molendini L, Sollazzo MR, Pompetti F, Merli M, Magagnoli G, Balladelli A, Picci P (1998) C-myc and c-fos in human osteosarcoma: prognostic value of mRNA and protein expression. Oncology 55(6):556–563PubMedCrossRef
25.
Zurück zum Zitat Pompetti F, Rizzo P, Simon RM, Freidlin B, Mew DJ, Pass HI, Picci P, Levine AS, Carbone M (1996) Oncogene alterations in primary, recurrent, and metastatic human bone tumors. J Cell Biochem 63(1):37–50PubMedCrossRef Pompetti F, Rizzo P, Simon RM, Freidlin B, Mew DJ, Pass HI, Picci P, Levine AS, Carbone M (1996) Oncogene alterations in primary, recurrent, and metastatic human bone tumors. J Cell Biochem 63(1):37–50PubMedCrossRef
26.
Zurück zum Zitat Takayama K, Ueno H, Nakanishi Y, Sakamoto T, Inoue K, Shimizu K, Oohashi H, Hara N (2000) Suppression of tumor angiogenesis and growth by gene transfer of a soluble form of vascular endothelial growth factor receptor into a remote organ. Cancer Res 60(8):2169–2177PubMed Takayama K, Ueno H, Nakanishi Y, Sakamoto T, Inoue K, Shimizu K, Oohashi H, Hara N (2000) Suppression of tumor angiogenesis and growth by gene transfer of a soluble form of vascular endothelial growth factor receptor into a remote organ. Cancer Res 60(8):2169–2177PubMed
27.
Zurück zum Zitat Yang SY, Yu H, Krygier JE, Wooley PH, Mott MP (2007) High VEGF with rapid growth and early metastasis in a mouse osteosarcoma model. Sarcoma 2007:95628PubMedCrossRef Yang SY, Yu H, Krygier JE, Wooley PH, Mott MP (2007) High VEGF with rapid growth and early metastasis in a mouse osteosarcoma model. Sarcoma 2007:95628PubMedCrossRef
28.
Zurück zum Zitat Yin D, Jia T, Gong W, Yu H, Wooley PH, Mott MP, Yang SY (2008) VEGF blockade decelerates the growth of a murine experimental osteosarcoma. Int J Oncol 33(2):253–259PubMed Yin D, Jia T, Gong W, Yu H, Wooley PH, Mott MP, Yang SY (2008) VEGF blockade decelerates the growth of a murine experimental osteosarcoma. Int J Oncol 33(2):253–259PubMed
Metadaten
Titel
Expression of Vascular Endothelial Growth Factor correlates with the advance of clinical osteosarcoma
verfasst von
John Lammli
Minyan Fan
Howard G. Rosenthal
Meghan Patni
Elizabeth Rinehart
Gerardo Vergara
Elizabeth Ablah
Paul H. Wooley
George Lucas
Shang-You Yang
Publikationsdatum
01.11.2012
Verlag
Springer-Verlag
Erschienen in
International Orthopaedics / Ausgabe 11/2012
Print ISSN: 0341-2695
Elektronische ISSN: 1432-5195
DOI
https://doi.org/10.1007/s00264-012-1629-z

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