Influence of Tumor Microenvironment of Hepatocellular Carcinoma on the Proliferation of Vascular Endothelial Cells and Vascular Angiogenesis Ability_Journal of Biomedical Engineering

Authors：

XIAQing ¹ , YINHongmei ² , SHENYang ¹ , LIUJingxia ¹ , YANZhiping ¹ , HONGJinyong ¹ , ZHOUFating ¹ ,  LIUXiaoheng ¹

1. Institute of Biomedical Engineering, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China;
2. West China School of Pharmacy, Sichuan University, Chengdu 610041, China;

Corresponding author：

LIUXiaoheng, Email: liuxiaohg@scu.edu.cn

Keywords：

hepatocellular carcinoma; vascular endothelial cells; cell proliferation; angiogenesis

DOI：

10.7507/1001-5515.20150111

Video：

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Abstract Full text Figures/Tables Video References Cited by

To study the potential molecular mechanism of tumor angiogenesis in its microenvironment, we investigated the effects of HepG2 conditioned medium on the proliferation of vascular endothelial cell and vascular angiogenesis in our laboratory. Human umbilical vein endothelial EA.hy926 cells were co-cultured with HepG2 conditioned medium in vitro. The proliferation and the tubulogenesis of EA.hy926 cells were detected by teramethylazo salt azole (MTT) and tube formation assay, respectively. The results showed that the survival rate of the EA.hy926 cells was significantly increased under the co-culture condition. HepG2 conditioned medium also enhanced the angiogenesis ability of EA.hy926 cells. In addition, the expressions of intracellular VEGF and extracellular VEGFR (Flk-1) were regulated upward in a time-dependent manner. In conclusion, the proliferation of vascular endothelial cells and Vascula angiogenesis were improved under the condition of indirect co-culture.

Citation： XIAQing, YINHongmei, SHENYang, LIUJingxia, YANZhiping, HONGJinyong, ZHOUFating, LIUXiaoheng. Influence of Tumor Microenvironment of Hepatocellular Carcinoma on the Proliferation of Vascular Endothelial Cells and Vascular Angiogenesis Ability. Journal of Biomedical Engineering, 2015, 32(3): 612-617. doi: 10.7507/1001-5515.20150111 Copy

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15.	CABRERA R, NELSON D R. Review article:the management of hepatocellular carcinoma[J]. Aliment Pharmacol Ther, 2010, 31(4):461-476.
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17.	SEAVEY M M, MACIAG P C, AL-RAWI N, et al. An anti-vascular endothelial growth factor receptor 2/fetal liver kinase-1 Listeria monocytogenes anti-angiogenesis Cancer vaccine for the treatment of primary and metastatic Her-2/neu+breast tumors in a mouse model[J]. J Immunol, 2009, 182(9):5537-5546.
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21.	HICKLIN D J, ELLIS L M. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis[J]. J Clin Oncol, 2005, 23(5):1011-1027.

1. CROCI D O, SALATINO M. Tumor immune escape mechanisms that operate during metastasis[J]. Curr Pharm Biotechnol, 2011, 12(11):1923-1936.
2. ENGERS R, GABBERT H E. Mechanisms of tumor metastasis:cell biological aspects and clinical implications[J]. J Cancer Res Clin Oncol, 2000, 126(12):682-692.
3. CAIRNS R A, KHOKHA R, HILL R P. Molecular mechanisms of tumor invasion and metastasis:an integrated view[J]. Curr Mol Med, 2003, 3(7):659-671.
4. PRESSIANI T, BONI C, RIMASSA L, et al. Sorafenib in patients with Child-Pugh class A and B advanced hepatocellular carcinoma:a prospective feasibility analysis[J]. Ann Oncol, 2013, 24(2):406-411.
5. BISSELL M J, RADISKY D C, RIZKI A, et al. The organizing principle:microenvironmental influences in the normal and malignant breast[J]. Differentiation, 2002, 70(9/10):537-546.
6. TOI M, INADA K, SUZUKI H, et al. Tumor angiogenesis in breast cancer:its importance as a prognostic indicator and the association with vascular endothelial growth factor expression[J]. Breast Cancer Res Treat, 1995, 36(2):193-204.
7. MBEUNKUI F, JOHANN D J. Cancer and the tumor microenvironment:a review of an essential relationship[J]. Cancer Chemother Pharmacol, 2009, 63(4):571-582.
8. LEONARDI G C, CANDIDO S, CERVELLO M, et al. The tumor microenvironment in hepatocellular carcinoma (review)[J]. Int J Oncol, 2012, 40(6):1733-1747.
9. LOGES S, MAZZONE M, HOHENSINNER P, et al. Silencing or fueling metastasis with VEGF inhibitors:antiangiogenesis revisited[J]. Cancer Cell, 2009, 15(3):167-170.
10. NYBERG P, XIE L, KALLURI R. Endogenous inhibitors of angiogenesis[J]. Cancer Res, 2005, 65(10):3967-3979.
11. GARCIA A, KANDEL J J. Notch:a key regulator of tumor angiogenesis and metastasis[J]. Histol Histopathol, 2012, 27(2):151-156.
12. PRIOR B M, YANG H T, TERJUNG R L. What makes vessels grow with exercise training?[J]. J Appl Physiol, 2004, 97(3):1119-1128.
13. GOMES F G, NEDEL F, ALVES A M, et al. Tumor angiogenesis and lymphangiogenesis:tumor/endothelial crosstalk and cellular/microenvironmental signaling mechanisms[J]. Life Sci, 2013, 92(2):101-107.
14. KHODAREV N N, YU J, LABAY E, et al. Tumour-endothelium interactions in co-culture:coordinated changes of gene expression profiles and phenotypic properties of endothelial cells[J]. J Cell Sci, 2003, 116(Pt 6):1013-1022.
15. CABRERA R, NELSON D R. Review article:the management of hepatocellular carcinoma[J]. Aliment Pharmacol Ther, 2010, 31(4):461-476.
16. LIN Weiyang, HSU W H. Tumor-to-tumor metastasis:maxillary sinus adenoid cystic carcinoma metastasizing to double primary lung adenocarcinoma[J]. Ann Thorac Surg, 2010, 90(4):e59-e61.
17. SEAVEY M M, MACIAG P C, AL-RAWI N, et al. An anti-vascular endothelial growth factor receptor 2/fetal liver kinase-1 Listeria monocytogenes anti-angiogenesis Cancer vaccine for the treatment of primary and metastatic Her-2/neu+breast tumors in a mouse model[J]. J Immunol, 2009, 182(9):5537-5546.
18. CHEN Zhijian, HTAY A, DOS SANTOS W, et al. In vitro angiogenesis by human umbilical vein endothelial cells(HUVEC)induced by three-dimensional co-culture with glioblastoma cells[J]. J Neurooncol, 2009, 92(2):121-128.
19. YOSHIJI H, KURIYAMA S, HICKLIN D J, et al. The vascular endothelial growth factor receptor KDR/Flk-1 is a major regulator of malignant ascites formation in the mouse hepatocellular carcinoma model[J]. Hepatology, 2001, 33(4):841-847.
20. SHIBUYA M. Differential roles of vascular endothelial growth factor receptor-1 and receptor-2 in angiogenesis[J]. J Biochem Mol Biol, 2006, 39(5):469-478.
21. HICKLIN D J, ELLIS L M. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis[J]. J Clin Oncol, 2005, 23(5):1011-1027.

Journal of Biomedical Engineering

Influence of Tumor Microenvironment of Hepatocellular Carcinoma on the Proliferation of Vascular Endothelial Cells and Vascular Angiogenesis Ability

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