Research Article
BibTex RIS Cite

Anjiyogenez Bağlantılı Büyüme Faktörleri VEGF-a ve FGF-1’in Osteosarkoma Hücre Proliferasyonu Üzerine Etkileri

Year 2020, Volume: 10 Issue: 2, 403 - 412, 30.12.2020
https://doi.org/10.37094/adyujsci.751882

Abstract

      Osteosarkoma çocuklar ve ergenlerde en sık görülen kemik tümörüdür. Bazı genlerin, sitokinlerin ve büyüme faktörlerinin ekspresyonundaki değişiklikler osteosarkomada malign fenotipin gelişiminden sorumludur. VEGF ve FGF ailelerinin bazı üyeleri, osteosarkomayı da içeren çeşitli tümör tiplerinde kötü prognoz ve metastaz ile ilişkilendirilmiştir. Ailenin üyelerinden VEGF-a ve FGF-1’in osteosarcoma hücre proliferasyonuna olan etkileri hakkında bilgiler sınırlıdır.
     Bu çalışmada VEGF-a ve FGF-1'in osteosarkoma hücre proliferasyonu üzerindeki etkilerinin aydınlatılması amaçlanmıştır. Osteosarkoma modeli olarak osteoblastik özelliklere sahip Saos-2 hücreleri kullanıldı. Hücreler, 24 saatlik serum açlığından sonra 20 ng/mL VEGF-a ve FGF-1 ile muamele edildi. 1-72 saat inkübasyon süresinden sonra hücre canlılığını ölçmek için MTT testi uygulandı. Sonuçlar VEGF-a’nın tüm inkübasyon süreleri için hücre proliferasyonunu arttırdığını gösterdi. Maksimum artış, istatistiksel olarak anlamlı bir şekilde, 48 saatlik inkübasyon (1.7 kat) süresinden sonra gözlendi. FGF-1, Saos-2 hücre proliferasyonunda çok küçük bir artışa yol açtı. Sonuç olarak, bu bulgular osteosarkom için yeni tedavi stratejilerinin geliştirilmesine katkıda bulunabilir.

References

  • [1] Shimizu, T., Ishikawa, T., Iwai, S., Ueki, A., Sugihara, E., Onishi, N., Kuninaka, S., Miyamoto, T., Toyama, Y., Ijiri, H., et al., Fibroblast growth factor-2 is an important factor that maintains cellular immaturity and contributes to aggressiveness of osteosarcoma, Molecular Cancer Research, 10, 454–468, 2012.
  • [2] Bielack, S.S., Kempf-Bielack, B., Delling, G., Exner, G.U., Flege, S., Helmke, K., et al., Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols, Journal of Clinical Oncology, 20,776–90, 2002.
  • [3] Clark, J.C.M., Dass, C.R., A review of clinical and molecular prognostic factors in osteosarcoma, Jornal of Cancer Research and Clinical Oncology,134, 281–97, 2008.
  • [4] Zhou, W.Y., Zheng, H., Du, X.L., Yang, J.L., Characterization of FGFR signaling pathway as therapeutic targets for sarcoma patients, Cancer Biology and Medicine, 13,260–8, 2016.
  • [5] Baird, K., Davis, S., Antonescu, C.R., Harper, U.L., Walker, R.L., Chen, Y., et al., Gene expression profiling of human sarcomas: Insights into sarcoma biology, Cancer Research, 65, 9226-35,2005.
  • [6] Xu, C.J., Song, J.F., Su, Y.X., Liu, X.L., Expression of b‐FGF and endostatin and their clinical significance in human osteosarcoma, Orthophedic Surgery, 2, 291– 8, 2010.
  • [7] Berhe, S,, Danzer, E., Meyer, P., Behr, G., LaQuaglia, M.P., Price, A.P., Unusual abdominal metastases in osteosarcoma , Journal of Pediatric Surgery Case Reports, 28, 13–16, 2018
  • [8] Shih, C.H., Chiang, T.B., Wang, W.J., Synergistic suppression of a disintegrin acurhagin-C in combination with AZD4547 and reparixin on terminating development for human osteosarcoma MG-63 cell, Biochemical and Biophysical Research Communications, 492, 513-519,2017.
  • [9] Mirabello, L., Troisi, R.J., Savage, S.A., International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons, International Jornal of Cancer, 125, 229-234, 2009.
  • [10] Li, Y., Zhang, J., Ma, D., et al., Curcumin inhibits proliferation and invasion of osteosarcoma cells through inactivation of Notch-1 signaling, FEBS Journal, 279(12), 2247–2259, 2012.
  • [11] Goldszmid, R.S., Trinchieri, G., The price of immunity. Nature Immunology, 13, 932-938, 2012.
  • [12] Turtle, C.J., Hudecek, M., Jensen, M.C., Riddell, S.R., Engineered T cells for anti-cancer therapy, Current Opinion in Immunology 24, 633-639, 2012.
  • [13] Dunlop, R.J., Campbell, C.W., Cytokines and advanced cancer, Journal of Pain and Symptom Management, 20 (3) ,214-232, 2000.
  • [14] Negus, R.P.M., Balkwill, F.R., Cytokines in tumour growth, migration and metastasis. World Journal of Urology, 14,157–165, 1996.
  • [15] Zumkeller, W., Schofield, P.N., Growth factors, cytokines and soluble forms of receptor molecules in cancer patients, Anticancer Research, 15, 344–348,1995.
  • [16]. Fridman, W.H., Tartour, E., The use of cytokines in the treatment of solid tumours. Haematolgy, Transfusion and Cell Therapy, 39,105–108, 1997 . [17] Savitskaya, Y.A., Rico-Martínez, G., Linares-González, L.M., Delgado-Cedillo, E.A., Téllez-Gastelum, R., Alfaro-Rodríguez, A.B., et al., Serum tumor markers in pediatric osteosarcoma: a summary review, Clinical Sarcoma Research, 2, 9, 2012
  • [18] Koch., S., Claesson-Welsh, L., Signal transduction by vascular endothelial growth factor receptors, Cold Spring Harbor Perspectives in Medicine, 2, a006502, 2012.
  • [19] Carmeliet, P., Jain, R.K., Angiogenesis in cancer and other diseases, Nature 407, 249–257, 2000.
  • [20] Folkman, J., Role of angiogenesis in tumor growth and metastasis, Seminars in Oncology, 29, 15–18, 2002.
  • [21] Ferrara, N., Carver-Moore, K., Chen, H., Dowd, M., Lu, L., O'Shea, K.S., et al., Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene, Nature, 380,439-442, 1996.
  • [22] Ahluwalia, A., Jones, M.K., Matysiak-Budnik, T., Tarnawski, A.S., VEGF and colon cancer growth beyond angiogenesis: does VEGF directly mediate colon cancer growth via a non-angiogenic mechanism? Current Pharmaceutical Design, 20,1041-1044, 2014.
  • [23] Hata, K., Watanabe, Y., Nakai, H., Hata, T., Hoshiai, H., Expression of the vascular endothelial growth factor (VEGF) gene in epithelial ovarian cancer: an approach to anti-VEGF therapy, Anticancer Research, 31, 731-737, 2011.
  • [24] Yu, X.W., Wu, T.Y., Yi, X., Ren, W.P., Zhou, Z.B., Sun, Y.Q., et al., Prognostic significance of VEGF expression in osteosarcoma: a meta-analysis, Tumor Biology, 35,155-160, 2014.
  • [25] Zhuang, Y., Wei, M., Impact of vascular endothelial growth factor expression on overall survival in patients with osteosarcoma: a meta-analysis, Tumor Biology, 35, 1745-1749, 2014.
  • [26] Han, G., Wang, Y., Bi, W., Jia, J., Wang, W., Xu, M., Effects of vascular endothelial growth factor expression on pathological characteristics and prognosis of osteosarcoma, Clinical and Experimental Medicine, 16(4), 577-584, 2016.
  • [27] Matsumoto, G., Hirohata, R., Hayashi, K., Sugimoto, Y., Kotani, E., Shimabukuro, J., Hirano, T., Nakajima, Y., Kawamata, S., Mori, H., Control of angiogenesis by VEGF and endostatin-encapsulated protein microcrystals and inhibition of tumor angiogenesis, Biomaterials, 35, 1326-33, 2014.
  • [28] Baptista, A.M., Camargo, A.F., Filippi, R.Z., Oliveira, C.R., Azevedo Neto, R.S., Camargo, O.P., Correlation between the expression of vegf and survival in osteosarcoma, Acta Ortopedica Brasileria, 22, 250-5,2014
  • [29] Peng, N., Gao, S., Guo, X., et al., Silencing of VEGF inhibits human osteosarcoma angiogenesis and promotes cell apoptosis via VEGF/PI3K/AKT signaling pathway, American Journal of Translational Research, 8(2),1005–1015, 2016.
  • [30] Dai, S., Zhou, Z., Chen, Z., Xu, G., Chen, Y., Fibroblast Growth Factor Receptors (FGFRs): Structures and Small Molecule Inhibitors, Cells, 8(6), 614, 2019.
  • [31] Ramos, C., Becerril, C., Montano, M., Garcia-De-Alba, C., Ramirez, R., Checa, M., et al., FGF-1 reverts epithelial mesenchymal transition induced by TGF-{beta}1 through MAPK/ERK kinase pathway, American Journal of Physiolgy Lung Cellular and Molecular Physiolgy, 299, L222-31, 2010.
  • [32] Jouanneau, J., Plouet, J., Moens, G., Thiery, J.P., FGF-2 and FGF-1 expressed in rat bladder carcinoma cells have similar angiogenic potential but different tumorigenic properties in vivo, Oncogene, 14, 671-6, 1997.
  • [33] Chudzian, J., Szlachcic, A., Zakrzewska, M., et al., Specific Antibody Fragment Ligand Traps Blocking FGF1 Activity, International Journal of Molecular Sciences, 19 (9),2470, 2018.
  • [34] Han, D., Wang, M., Yu, Z., Yin, L., Liu, C., Wang, J., Liu, Y., Jiang, S., Ren, Z., & Yin, J., FGF5 promotes osteosarcoma cells proliferation via activating MAPK signaling pathway. Cancer management and research, 11, 6457–6466, 2019.
  • [35] Alper, M., Aydemir, A.T., Köçkar, F., Induction of Human ADAMTS-2 Gene Expression by IL-1α is Mediated by a Multiple Crosstalk of MEK/JNK and PI3K Pathways in Osteoblast like Cells,Gene, 573 (2),321-7, 2015.
  • [36] Kim, H.Y., Analysis of variance (ANOVA) comparing means of more than two groups. Restorative dentistry & endodontics, 39(1), 74–77, 2014.
  • [37] Fogh, J., Fogh, J.M., Orfeo, T, One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice, Journal of the National Cancer Institute, 59(1), 221–226, 1977.
  • [38] McQuillan, D.J., Richardson, M.D., Bateman, J.F., Matrix deposition by a calcifying human osteogenic sarcoma cell line (SAOS- 2), Bone, 16 (4), 415–26, 1995.
  • [39] Lu, X., Tao, J., Wei, G., Anti-angiogenesis target therapy for advanced osteosarcoma, Oncology Reports, 38,625-636, 2017.
  • [40]. Hicklin, D.J., Ellis, L.M., Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis, Journal of Clinical Oncology, 23, 1011–1027, 2005.

Effect of Angiogenesis Related Growth Factors VEGF-a and FGF-1 on Osteosarcoma Cell Proliferation

Year 2020, Volume: 10 Issue: 2, 403 - 412, 30.12.2020
https://doi.org/10.37094/adyujsci.751882

Abstract

      Osteosarcoma is the most common bone tumor in children and adolescents. Alterations in the expression of some genes, cytokines and growth factors are responsible for the development of the malignant phenotype in osteosarcoma. Some members of the VEGF and FGF families have been associated with poor prognosis and the metastasis in various tumor types including osteosarcoma. Among the members of the family, information about effects of VEGF-a and FGF- 1 on osteosarcoma cell proliferation is limited.

      In the present study, it was aimed to elucidate the effects of VEGF-a and FGF-1 on osteosarcoma cell proliferation. Saos-2 cells, having osteoblastic features, were used for osteosarcoma model. Cells were treated 20 ng/mL VEGF-a and FGF-1 after 24 hours of serum starvation. MTT assay was applied to measure cell viability after incubation for 1-72 hours. Results indicated that VEGF-a promoted cell proliferation for all incubation times. Maximum increase was observed after 48 hours of incubation (1.7 fold) with a statistically important manner. FGF-1 led to very slight increase in Saos-2 cell proliferation. Consequently, these findings can contribute development of new therapy strategies for osteosarcoma.

References

  • [1] Shimizu, T., Ishikawa, T., Iwai, S., Ueki, A., Sugihara, E., Onishi, N., Kuninaka, S., Miyamoto, T., Toyama, Y., Ijiri, H., et al., Fibroblast growth factor-2 is an important factor that maintains cellular immaturity and contributes to aggressiveness of osteosarcoma, Molecular Cancer Research, 10, 454–468, 2012.
  • [2] Bielack, S.S., Kempf-Bielack, B., Delling, G., Exner, G.U., Flege, S., Helmke, K., et al., Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols, Journal of Clinical Oncology, 20,776–90, 2002.
  • [3] Clark, J.C.M., Dass, C.R., A review of clinical and molecular prognostic factors in osteosarcoma, Jornal of Cancer Research and Clinical Oncology,134, 281–97, 2008.
  • [4] Zhou, W.Y., Zheng, H., Du, X.L., Yang, J.L., Characterization of FGFR signaling pathway as therapeutic targets for sarcoma patients, Cancer Biology and Medicine, 13,260–8, 2016.
  • [5] Baird, K., Davis, S., Antonescu, C.R., Harper, U.L., Walker, R.L., Chen, Y., et al., Gene expression profiling of human sarcomas: Insights into sarcoma biology, Cancer Research, 65, 9226-35,2005.
  • [6] Xu, C.J., Song, J.F., Su, Y.X., Liu, X.L., Expression of b‐FGF and endostatin and their clinical significance in human osteosarcoma, Orthophedic Surgery, 2, 291– 8, 2010.
  • [7] Berhe, S,, Danzer, E., Meyer, P., Behr, G., LaQuaglia, M.P., Price, A.P., Unusual abdominal metastases in osteosarcoma , Journal of Pediatric Surgery Case Reports, 28, 13–16, 2018
  • [8] Shih, C.H., Chiang, T.B., Wang, W.J., Synergistic suppression of a disintegrin acurhagin-C in combination with AZD4547 and reparixin on terminating development for human osteosarcoma MG-63 cell, Biochemical and Biophysical Research Communications, 492, 513-519,2017.
  • [9] Mirabello, L., Troisi, R.J., Savage, S.A., International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons, International Jornal of Cancer, 125, 229-234, 2009.
  • [10] Li, Y., Zhang, J., Ma, D., et al., Curcumin inhibits proliferation and invasion of osteosarcoma cells through inactivation of Notch-1 signaling, FEBS Journal, 279(12), 2247–2259, 2012.
  • [11] Goldszmid, R.S., Trinchieri, G., The price of immunity. Nature Immunology, 13, 932-938, 2012.
  • [12] Turtle, C.J., Hudecek, M., Jensen, M.C., Riddell, S.R., Engineered T cells for anti-cancer therapy, Current Opinion in Immunology 24, 633-639, 2012.
  • [13] Dunlop, R.J., Campbell, C.W., Cytokines and advanced cancer, Journal of Pain and Symptom Management, 20 (3) ,214-232, 2000.
  • [14] Negus, R.P.M., Balkwill, F.R., Cytokines in tumour growth, migration and metastasis. World Journal of Urology, 14,157–165, 1996.
  • [15] Zumkeller, W., Schofield, P.N., Growth factors, cytokines and soluble forms of receptor molecules in cancer patients, Anticancer Research, 15, 344–348,1995.
  • [16]. Fridman, W.H., Tartour, E., The use of cytokines in the treatment of solid tumours. Haematolgy, Transfusion and Cell Therapy, 39,105–108, 1997 . [17] Savitskaya, Y.A., Rico-Martínez, G., Linares-González, L.M., Delgado-Cedillo, E.A., Téllez-Gastelum, R., Alfaro-Rodríguez, A.B., et al., Serum tumor markers in pediatric osteosarcoma: a summary review, Clinical Sarcoma Research, 2, 9, 2012
  • [18] Koch., S., Claesson-Welsh, L., Signal transduction by vascular endothelial growth factor receptors, Cold Spring Harbor Perspectives in Medicine, 2, a006502, 2012.
  • [19] Carmeliet, P., Jain, R.K., Angiogenesis in cancer and other diseases, Nature 407, 249–257, 2000.
  • [20] Folkman, J., Role of angiogenesis in tumor growth and metastasis, Seminars in Oncology, 29, 15–18, 2002.
  • [21] Ferrara, N., Carver-Moore, K., Chen, H., Dowd, M., Lu, L., O'Shea, K.S., et al., Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene, Nature, 380,439-442, 1996.
  • [22] Ahluwalia, A., Jones, M.K., Matysiak-Budnik, T., Tarnawski, A.S., VEGF and colon cancer growth beyond angiogenesis: does VEGF directly mediate colon cancer growth via a non-angiogenic mechanism? Current Pharmaceutical Design, 20,1041-1044, 2014.
  • [23] Hata, K., Watanabe, Y., Nakai, H., Hata, T., Hoshiai, H., Expression of the vascular endothelial growth factor (VEGF) gene in epithelial ovarian cancer: an approach to anti-VEGF therapy, Anticancer Research, 31, 731-737, 2011.
  • [24] Yu, X.W., Wu, T.Y., Yi, X., Ren, W.P., Zhou, Z.B., Sun, Y.Q., et al., Prognostic significance of VEGF expression in osteosarcoma: a meta-analysis, Tumor Biology, 35,155-160, 2014.
  • [25] Zhuang, Y., Wei, M., Impact of vascular endothelial growth factor expression on overall survival in patients with osteosarcoma: a meta-analysis, Tumor Biology, 35, 1745-1749, 2014.
  • [26] Han, G., Wang, Y., Bi, W., Jia, J., Wang, W., Xu, M., Effects of vascular endothelial growth factor expression on pathological characteristics and prognosis of osteosarcoma, Clinical and Experimental Medicine, 16(4), 577-584, 2016.
  • [27] Matsumoto, G., Hirohata, R., Hayashi, K., Sugimoto, Y., Kotani, E., Shimabukuro, J., Hirano, T., Nakajima, Y., Kawamata, S., Mori, H., Control of angiogenesis by VEGF and endostatin-encapsulated protein microcrystals and inhibition of tumor angiogenesis, Biomaterials, 35, 1326-33, 2014.
  • [28] Baptista, A.M., Camargo, A.F., Filippi, R.Z., Oliveira, C.R., Azevedo Neto, R.S., Camargo, O.P., Correlation between the expression of vegf and survival in osteosarcoma, Acta Ortopedica Brasileria, 22, 250-5,2014
  • [29] Peng, N., Gao, S., Guo, X., et al., Silencing of VEGF inhibits human osteosarcoma angiogenesis and promotes cell apoptosis via VEGF/PI3K/AKT signaling pathway, American Journal of Translational Research, 8(2),1005–1015, 2016.
  • [30] Dai, S., Zhou, Z., Chen, Z., Xu, G., Chen, Y., Fibroblast Growth Factor Receptors (FGFRs): Structures and Small Molecule Inhibitors, Cells, 8(6), 614, 2019.
  • [31] Ramos, C., Becerril, C., Montano, M., Garcia-De-Alba, C., Ramirez, R., Checa, M., et al., FGF-1 reverts epithelial mesenchymal transition induced by TGF-{beta}1 through MAPK/ERK kinase pathway, American Journal of Physiolgy Lung Cellular and Molecular Physiolgy, 299, L222-31, 2010.
  • [32] Jouanneau, J., Plouet, J., Moens, G., Thiery, J.P., FGF-2 and FGF-1 expressed in rat bladder carcinoma cells have similar angiogenic potential but different tumorigenic properties in vivo, Oncogene, 14, 671-6, 1997.
  • [33] Chudzian, J., Szlachcic, A., Zakrzewska, M., et al., Specific Antibody Fragment Ligand Traps Blocking FGF1 Activity, International Journal of Molecular Sciences, 19 (9),2470, 2018.
  • [34] Han, D., Wang, M., Yu, Z., Yin, L., Liu, C., Wang, J., Liu, Y., Jiang, S., Ren, Z., & Yin, J., FGF5 promotes osteosarcoma cells proliferation via activating MAPK signaling pathway. Cancer management and research, 11, 6457–6466, 2019.
  • [35] Alper, M., Aydemir, A.T., Köçkar, F., Induction of Human ADAMTS-2 Gene Expression by IL-1α is Mediated by a Multiple Crosstalk of MEK/JNK and PI3K Pathways in Osteoblast like Cells,Gene, 573 (2),321-7, 2015.
  • [36] Kim, H.Y., Analysis of variance (ANOVA) comparing means of more than two groups. Restorative dentistry & endodontics, 39(1), 74–77, 2014.
  • [37] Fogh, J., Fogh, J.M., Orfeo, T, One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice, Journal of the National Cancer Institute, 59(1), 221–226, 1977.
  • [38] McQuillan, D.J., Richardson, M.D., Bateman, J.F., Matrix deposition by a calcifying human osteogenic sarcoma cell line (SAOS- 2), Bone, 16 (4), 415–26, 1995.
  • [39] Lu, X., Tao, J., Wei, G., Anti-angiogenesis target therapy for advanced osteosarcoma, Oncology Reports, 38,625-636, 2017.
  • [40]. Hicklin, D.J., Ellis, L.M., Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis, Journal of Clinical Oncology, 23, 1011–1027, 2005.
There are 39 citations in total.

Details

Primary Language English
Subjects Structural Biology
Journal Section Biology
Authors

Meltem Alper 0000-0001-6359-9979

Publication Date December 30, 2020
Submission Date June 12, 2020
Acceptance Date September 10, 2020
Published in Issue Year 2020 Volume: 10 Issue: 2

Cite

APA Alper, M. (2020). Effect of Angiogenesis Related Growth Factors VEGF-a and FGF-1 on Osteosarcoma Cell Proliferation. Adıyaman University Journal of Science, 10(2), 403-412. https://doi.org/10.37094/adyujsci.751882
AMA Alper M. Effect of Angiogenesis Related Growth Factors VEGF-a and FGF-1 on Osteosarcoma Cell Proliferation. ADYU J SCI. December 2020;10(2):403-412. doi:10.37094/adyujsci.751882
Chicago Alper, Meltem. “Effect of Angiogenesis Related Growth Factors VEGF-a and FGF-1 on Osteosarcoma Cell Proliferation”. Adıyaman University Journal of Science 10, no. 2 (December 2020): 403-12. https://doi.org/10.37094/adyujsci.751882.
EndNote Alper M (December 1, 2020) Effect of Angiogenesis Related Growth Factors VEGF-a and FGF-1 on Osteosarcoma Cell Proliferation. Adıyaman University Journal of Science 10 2 403–412.
IEEE M. Alper, “Effect of Angiogenesis Related Growth Factors VEGF-a and FGF-1 on Osteosarcoma Cell Proliferation”, ADYU J SCI, vol. 10, no. 2, pp. 403–412, 2020, doi: 10.37094/adyujsci.751882.
ISNAD Alper, Meltem. “Effect of Angiogenesis Related Growth Factors VEGF-a and FGF-1 on Osteosarcoma Cell Proliferation”. Adıyaman University Journal of Science 10/2 (December 2020), 403-412. https://doi.org/10.37094/adyujsci.751882.
JAMA Alper M. Effect of Angiogenesis Related Growth Factors VEGF-a and FGF-1 on Osteosarcoma Cell Proliferation. ADYU J SCI. 2020;10:403–412.
MLA Alper, Meltem. “Effect of Angiogenesis Related Growth Factors VEGF-a and FGF-1 on Osteosarcoma Cell Proliferation”. Adıyaman University Journal of Science, vol. 10, no. 2, 2020, pp. 403-12, doi:10.37094/adyujsci.751882.
Vancouver Alper M. Effect of Angiogenesis Related Growth Factors VEGF-a and FGF-1 on Osteosarcoma Cell Proliferation. ADYU J SCI. 2020;10(2):403-12.

...