Browse > Article
http://dx.doi.org/10.4062/biomolther.2021.062

A Synthetic Analog of Resveratrol Inhibits the Proangiogenic Response of Liver Sinusoidal Cells during Hepatic Metastasis  

Olaso, Elvira (Tumor Microenvironment Group, Department of Cell Biology and Histology, School of Medicine and Dentistry, University of the Basque Country)
Benedicto, Aitor (Tumor Microenvironment Group, Department of Cell Biology and Histology, School of Medicine and Dentistry, University of the Basque Country)
Lopategi, Aritz (Tumor Microenvironment Group, Department of Cell Biology and Histology, School of Medicine and Dentistry, University of the Basque Country)
Cossio, Fernando P. (Department of Organic Chemistry, School of Sciences, University of the Basque Country)
Arteta, Beatriz (Tumor Microenvironment Group, Department of Cell Biology and Histology, School of Medicine and Dentistry, University of the Basque Country)
Publication Information
Biomolecules & Therapeutics / v.30, no.2, 2022 , pp. 162-169 More about this Journal
Abstract
We utilized Fas21, a resveratrol analog, to modulate the function of hepatic stellate cells (HSCs) and liver sinusoidal endothelial cells (LSECs) during the angiogenic phase of murine liver metastasis by B16 melanoma and 51b colorectal carcinoma. Preangiogenic micrometastases were treated with Fas21 (1 mg/kg/day) or vehicle during the development of intra-angiogenic tracts. Mice treated with Fas21 showed reduced liver tumor foci in both liver metastasis models. Micrometastases were classified immunohistochemically, as well as according to their position coordinates and connection to local microvasculature. The volume of liver occupied by sinusoidal-type foci, containing infiltrating angiogenic capillaries, decreased by ~50% in Fas21-treated mice compared to vehicle-treated ones in both tumor metastasis models. The volume of portal foci, containing peripheral neoangiogenesis within a discontinuous layer of myofibroblasts, was similar in all experimental groups in both tumor metastasis models, but displayed enhanced necrotic central areas devoid of angiogenesis following Fas21 treatment. As a result, sinusoidal tumors from mice treated with Fas21 showed a 50% reduction in desmin(+)/asma(+) HSCs and CD31(+) vessel density, and a 45% reduction in intrametastatic VEGF mRNA compared with sinusoidal tumors from vehicle-treated mice. Necrotic portal metastases increased 2-4-fold in treated mice. In vitro, Fas21 reduced VEGF secretion by HSCs and 51b cells dose-dependently. Additionally, HSCs migration in response to tumor soluble factors was dose-dependently diminished by Fas21, as was LSEC migration in response to HSCs and tumor soluble factors. Resveratrol analog Fas21 inhibits the proangiogenic response of HSCs and LSECs during the development of murine liver metastasis.
Keywords
Hepatic stellate cell; Liver sinusoidal endothelial cell; Liver metastasis; Tumor microenvironment; Angiogenesis; Cancer;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Grimme, S., Ehrlich, S. and Goerigk, L. (2011) Effect of the damping function in dispersion corrected density functional theory. J. Comput. Chem. 32, 1456-1465.   DOI
2 Salado, C., Olaso, E., Gallot, N., Valcarcel, M., Egilegor, E., Mendoza, L. and Vidal-Vanaclocha, F. (2011) Resveratrol prevents inflammation-dependent hepatic melanoma metastasis by inhibiting the secretion and effects of interleukin-18. J. Transl. Med. 9, 59.   DOI
3 Shimizu, S., Yamada, N., Sawada, T., Ikeda, K., Kawada, N., Seki, S., Kaneda, K. and Hirakawa, K. (2000) In vivo and in vitro interactions between human colon carcinoma cells and hepatic stellate cells. Jpn. J. Cancer Res. 91, 1285-1295.   DOI
4 Stephens, P. J., Deviln, F. J., Chabalowski, C. F. and Frisch, M. J. (1994) Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields. J. Phys. Chem. 98, 11623-11627.   DOI
5 Brakenhielm, E., Cao, R. and Cao, Y. (2001) Suppression of angiogenesis, tumor growth, and wound healing by resveratrol, a natural compound in red wine and grapes. FASEB J. 15, 1798-1800.   DOI
6 Cossio, F., Aldaba, E., Vara, Y., Zubia, A., Vivanco, S., Mendoza, L., Salado, C., Gallot, N. and Vidal-Banaclocha, F. (2006) New nitrogen-containing trans-stilbene analogs and their preparation, antimetastatic activity and their medical applications. United States Patent US 20,110,060,038. 2006 Oct 19.
7 Cushman , M., Georg, G. I., Holzgrabe, U. and Wang, S. (2014) Absolute quantitative 1H NMR spectroscopy for compound purity determination. J. Med. Chem. 57, 9219.   DOI
8 Solaun, M. S., Mendoza, L., De Luca, M., Gutierrez, V., Lopez, M. P., Olaso, E., Sim, B. K. L. and Vidal-Vanaclocha, F. (2002) Endostatin inhibits murine colon carcinoma sinusoidal-type metastases by preferential targeting of hepatic sinusoidal endothelium. Hepatology 35, 1104-1116.   DOI
9 Vidal-Vanaclocha, F. (2008) The prometastatic microenvironment of the liver. Cancer Microenviron. 1, 113-129.   DOI
10 Olaso, E., Salado, C., Egilegor, E., Gutierrez, V., Santisteban, A., SanchoBru, P., Friedman, S. L. and Vidal-Vanaclocha, F. (2003) Proangiogenic role of tumor-activated hepatic stellate cells in experimental melanoma metastasis. Hepatology 37, 674-685.   DOI
11 Delmas, D., Lancon, A., Colin, D., Jannin, B. and Latruffe, N. (2006) Resveratrol as a chemopreventive agent: a promising molecule for fighting cancer. Curr. Drug Targets 7, 423-442   DOI
12 Arteta, B., Lasuen, N., Lopategi, A., Sveinbjornsson, B., Smedsrod, B. and Vidal-Vanaclocha, F. (2010) Colon carcinoma cell interaction with liver sinusoidal endothelium inhibits organ-specific antitumor immunity through interleukin-1-induced mannose receptor in mice. Hepatology 51, 2172-2182.   DOI
13 Becke, A. D. (1993) Density-functional thermochemistry. III. The role of exact exchange. J. Chem. Phys. 98, 5648.   DOI
14 Bresalier, R. S., Hujanes, E. S., Raper, S. E., Roll, F. J., Itzkowitz, S. H., Martin, G. R. and Kim, Y. S. (1987) An animal model for colon cancer metastasis: establishment and characterization of murine cell lines with enhanced liver-metastasizing ability. Cancer Res. 47, 1398-1406.
15 Gulubova, M. V. (2004) Collagen type IV, laminin, alpha-smooth muscle actin (alphaSMA), alpha1 and alpha6 integrins expression in the liver with metastases from malignant gastrointestinal tumours. Clin. Exp. Metastasis 21, 485-494.   DOI
16 Hehre, W. J., Radom, L., Schleyer, P. R. and Pople, J. A. (1986) AB INITIO Molecular Orbital Theory. Wiley, New York.
17 Kundu, J. K. and Surh, Y. J. (2004) Molecular basis of chemoprevention by Resveratrol: NF-kappaB and AP-1 as potential targets. Mutat. Res. 555, 65-80.   DOI
18 Lee, E. S., Shin, M. O., Yoon, S. and Moon, J. O. (2010) Resveratrol inhibits dimethylnitrosamine-induced hepatic fibrosis in rats. Arch. Pharm. Res. 33, 925-932.   DOI
19 Makino, Y., Hikita, H., Kodama, T., Shigekawa, M., Yamada, R., Sakamori, R., Eguchi, H., Morii, E., Yokoi, H., Mukoyama, M., Hiroshi, S., Tatsumi, T. and Takehara, T. (2018) CTGF mediates tumor-stroma interactions between hepatoma cells and hepatic stellate cells to accelerate HCC progression. Cancer Res. 78, 4902-4914.   DOI
20 Lu, J., Li, C., Chai, Y. F., Yang, D. Y. and Sun, C. R. (2012) The antioxidant effect of imine resveratrol analogues. Bioorg. Med. Chem. Lett. 22, 5744-5747.   DOI
21 Weinhold, F. (2012) Natural bond orbital analysis: a critical overview of relationships to alternative bonding perspectives. J. Comput. Chem. 33, 2363-2379.   DOI
22 Herrero, A., Benedicto, A., Romayor, I., Olaso, E. and Arteta, B. (2021) Inhibition of COX-2 impairs colon cancer liver metastasis through reduced stromal cell reaction. Biomol. Ther. (Seoul) 29, 342-351.   DOI
23 Smedsrod, B. and Pertoft, H. (1985) Preparation of pure hepatocytes and reticuloendothelial cells in high yield from a single rat liver by means of Percoll centrifugation and selective adherence. J. Leukoc. Biol. 38, 213-230.   DOI
24 Mezawa, Y and Orino, A. (2016) The roles of tumor- and metastasis-promoting carcinoma-associated fibroblasts in human carcinomas. Cell Tissue Res. 365, 675-689.   DOI
25 Olaso, E., Santisteban, A., Bidaurrazaga, J., Gressner, A. M., Rosenbaum, J. and Vidal-Vanaclocha, F. (1997) Tumor-dependent activation of rodent hepatic stellate cells during experimental melanoma metastasis. Hepatology 26, 634-642.   DOI
26 Romayor, I., Badiola, I., Benedicto, A., Marquez, J., Herrero, A., Arteta, B. and Olaso, E. (2020) Silencing of sinusoidal DDR1 reduces murine liver metastasis by colon carcinoma. Sci. Rep. 10, 18398.   DOI
27 Barry, A. E., Baldeosingh, R., Lamm, R., Patel, K., Zhang, K., Dominguez, D. A., Kirton, K. J., Shah, A. P. and Dang, H. (2020) Hepatic stellate cells and hepatocarcinogenesis. Front. Cell Dev. Biol. 8, 709.   DOI
28 Walter, A., Etienne-Selloum, N., Brasse, D., Khallouf, H., Bronner, C., Rio, M. C., Beretz, A. and Schini-Kerth, V. B. (2008) Intake of grape-derived polyphenols reduces C26 tumor growth by inhibiting angiogenesis and inducing apoptosis. FASEB J. 24, 3360-3369.   DOI