[en] Tumor metastases, the most fearsome aspect of cancer, are generally resistant to conventional therapies. Angiogenesis is a crucial aspect of tumor growth and metastatic dissemination. Antiangiogenic therapy, therefore, holds potential as an attractive strategy for inhibiting metastasis development. Human 16K PRL (16K hPRL), a potent inhibitor of angiogenesis, has been demonstrated to prevent tumor growth in two xenograft mouse models, but whether it also affects tumor metastasis is unknown. In this study we will investigate the ability of 16K hPRL to prevent the establishment of metastasis. We demonstrate that 16K hPRL administered via adenovirus-mediated gene transfer, inhibits tumor growth by 86% in a subcutaneous (SC) B16-F10 mouse melanoma model. Computer-assisted image analysis shows that 16K hPRL treatment results in a reduction of tumor-vessel length and width, leading to a 57% reduction of average vessel size. In a pre-established tumor model, moreover, 16K hPRL can significantly delay tumor development. Finally, for the first time, we provide evidence that 16K hPRL considerably reduces the establishment of B16-F10 metastasis in an experimental lung metastasis model. Both the number and size of metastases are reduced by 50% in 16K hPRL-treated mice. These results highlight a potential role for 16K hPRL in anticancer therapy for both primary tumors and metastases.
Nguyen, Ngoc-Quynh-Nhu ; Université de Liège - ULiège > Département des sciences de la vie > Biologie et génétique moléculaire
Cornet, Anne ; Université de Liège - ULiège > Département de morphologie et pathologie > Pathologie spéciale et autopsies
Blacher, Silvia ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Tabruyn, Sébastien ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique
Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Martial, Joseph ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Struman, Ingrid ; Université de Liège - ULiège > Département des sciences de la vie > Biologie et génétique moléculaire
Language :
English
Title :
Inhibition of tumor growth and metastasis establishment by adenovirus-mediated gene transfer delivery of the antiangiogenic factor 16K hPRL
Publication date :
December 2007
Journal title :
Molecular Therapy
ISSN :
1525-0016
eISSN :
1525-0024
Publisher :
Nature Publishing Group, San Diego, United States - California
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
Bibliography
Steeg, PS (2006). Tumor metastasis: Mechanistic insights and clinical challenges. Nat Med 12: 895-904.
Fidler, IJ (2002). Critical determinants of metastasis. Semin Cancer Biol 12: 89-96.
Carmeliet, P (2005). Angiogenesis in life, disease and medicine. Nature 438: 932-936.
Zetter, BR (1998). Angiogenesis and tumor metastasis. Annu Rev Med 49: 407-424.
Ferrara, N and Kerbel, RS (2005). Angiogenesis as a therapeutic target. Nature 438: 967-974.
D'Angelo, G, Struman, I, Martial, JA and Weiner, RI (1995). Activation of mitogen-activated protein kinases by vascular endothelial growth factor and basic fibroblast growth factor in capillary endothelial cells is inhibited by the antiangiogenic factor 16-kDa N-terminal fragment of prolactin. Proc Natl Acad Sci USA 92: 6374-6378.
D'Angelo, G, Martini, JF, Iiri, T, Fantl, WJ, Martial, JA and Weiner, RI (1999). 16K human prolactin inhibits vascular endothelial growth factor-induced activation of Ras in capillary endothelial cells. Mol Endocrinol 13: 692-704.
Lee, H, Struman, I, Clapp, C, Martial, JA and Weiner, RI (1998). Inhibition of urokinase activity by the antiangiogenic factor 16K prolactin: Activation of plasminogen activator inhibitor 1 expression. Endocrinology 139: 3696-3703.
Martini, JF, Piot, C, Humeau, LM, Struman, I, Martial, JA and Weiner, RI (2000). The antiangiogenic factor 16K PRL induces programmed cell death in endothelial cells by caspase activation. Mol Endocrinol 14 1536-1549.
Tabruyn, SP, Sorlet, CM, Rentier-Delrue, F, Bours, V, Weiner, RI, Martial, JA et al. (2003). The antiangiogenic factor 16K human prolactin induces caspase-dependent apoptosis by a mechanism that requires activation of nuclear factor-κB. Mol Endocrinol 17 1815-1823.
Tabruyn, SP, Nguyen, NQ, Comet, AM, Martial, JA and Struman, I (2005). The antiangiogenic factor, 16-kDa human prolactin, induces endothelial cell cycle arrest by acting at both the G0-G1 and the G2-M phases. Mol Endocrinol 19: 1932-1942.
Hiffiker-Kleiner, D, Kaminski, K, Podewski, E, Bonda, T, Schaefer, A, Sliwa, K et al. (2007). A cathepsin D-cleaved 16kDa form of prolactin mediates postpartum cardiomyopathy. Cell 128: 589-600.
Bentzien, F, Struman, I, Martini, JF, Martial, JA and Weiner, RI (2001). Expression of the antiangiogenic factor 16K hPRL in human HCT116 colon cancer cells inhibits tumor growth in Rag1-/- mice. Cancer Res 61: 7356-7362.
Kim, J, Luo, W, Chen, DT, Earley, K, Tunstead, J, Yu-Lee, LY et al. (2003). Antitumor activity of the 16-kDa prolactin fragment in prostate cancer. Cancer Res 63: 386-393.
Pan, H, Nguyen, NQ, Yoshida, H, Bentzien, F, Shaw, LC, Rentier-Delrue, F et al. (2004). Molecular targeting of antiangiogenic factor 16K hPRL inhibits oxygen-induced retinopathy in mice. Invest Ophthalmol Vis Sci 45: 2413-2419.
Cao, Y (2001). Endogenous angiogenesis inhibitors and their therapeutic implications. Int J Biochem Cell Biol 33: 357-369.
Dkhissi, F, Lu, H, Soria, C, Opolon, P, Griscelli, F, Liu, H et al. (2003). Endostatin exhibits a direct antitumor effect in addition to its antiangiogenic activity in colon cancer cells. Hum Gene Ther 14: 997-1008.
Hajitou, A, Sounni, NE, Devy, L, Grignet-Debrus, C, Lewalle, JM, Li, H et al. (2001). Down-regulation of vascular endothelial growth factor by tissue inhibitor of metalloproteinase-2: Effect on in vivo mammary tumor growth and angiogenesis. Cancer Res 61: 3450-3457.
Streit, M, Riccardi, L, Velasco, P, Brown, LF, Hawighorst, T, Bornstein, P et al. (1999). Thrombospondin-2: A potent endogenous inhibitor of tumor growth and angiogenesis. Proc Natl Acad Sci USA 96: 14888-14893.
Blazquez, C, Casanova, ML, Planas, A, Del Pulgar, TG, Villanueva, C, Fernandez-Acenero, MJ et al. (2003). Inhibition of tumor angiogenesis by cannabinoids. FASEB J 17: 529-531.
Gonzalez, C, Corbacho, AM, Eiserich, JP, Garcia, C, Lopez-Barrera, F, Morales-Tialpan, V et al. (2004). 16K-prolactin inhibits activation of endothelial nitric oxide synthase, intracellular calcium mobilization, and endothelium-dependent vasorelaxation. Endocrinology 145: 5714-5722.
Woodhouse, EC, Chuaqui, RF and Liotta, LA (1997). General mechanisms of metastasis. Cancer 80(8 suppl.): 1529-1537.
Sauter, BV, Martinet, O, Zhang, WJ, Mandeli, J and Woo, SL (2000). Adenovirus-mediated gene transfer of endostatin in vivo results in high level of transgene expression and inhibition of tumor growth and metastases. Proc Natl Acad Sci USA 97: 4802-4807.
Lalani, AS, Ching, B, Lin, J, Case, SS, Luan, B, Wu-Prior, WW et al. (2004). Anti-tumor efficacy of human angiostatin using liver-mediated adeno-associated virus gene therapy. Mol Ther 9: 56-66.
Mah-Becherel, MC, Ceraline, J, Deplanque, G, Chenard, MP, Bergerat, JP, Cazenave, JP et al. (2002). Anti-angiogenic effects of the thienopyridine SR 25989 in vitro and in vivo in a murine pulmonary metastasis model. Br J Cancer 86: 803-810.
Niu, G, Xiong, Z, Cheng, Z, Cai, W, Gambhir, SS, Xing, L et al. (2007). In vivo bioluminescence tumor imaging of RGD peptide-modified adenoviral vector encoding firefly luciferase reporter gene. Mol Imaging Biol 9: 126-134.
Liu, Y, Koziol, J, Deisseroth, A and Borgstrom, P (2007). Methods for delivery of adenoviral vectors to tumor vasculature. Hum Gene Ther 18: 151-160.
Paris, N, Rentier-Delrue, F, Defontaine, A, Goffin, V, Lebrun, JJ, Mercier, L et al. (1990). Bacterial production and purification of recombinant human prolactin. Biotechnol Appl Biochem 12: 436-449.
Sun, J, Blaskovich, MA, Jain, RK, Delarue, F, Paris, D, Brem, S et al. (2004). Blocking angiogenesis and tumorigenesis with GFA-116, a synthetic molecule that inhibits binding of vascular endothelial growth factor to its receptor. Cancer Res 64: 3586-3592.
Sahoo, PK, Soltani, S, Wong, AKC and Chen, YC (1988). A survey of thresholding techniques. Comp Vis Graph Image Proc 41: 223-260.
Similar publications
Sorry the service is unavailable at the moment. Please try again later.
This website uses cookies to improve user experience. Read more
Save & Close
Accept all
Decline all
Show detailsHide details
Cookie declaration
About cookies
Strictly necessary
Performance
Strictly necessary cookies allow core website functionality such as user login and account management. The website cannot be used properly without strictly necessary cookies.
This cookie is used by Cookie-Script.com service to remember visitor cookie consent preferences. It is necessary for Cookie-Script.com cookie banner to work properly.
Performance cookies are used to see how visitors use the website, eg. analytics cookies. Those cookies cannot be used to directly identify a certain visitor.
Used to store the attribution information, the referrer initially used to visit the website
Cookies are small text files that are placed on your computer by websites that you visit. Websites use cookies to help users navigate efficiently and perform certain functions. Cookies that are required for the website to operate properly are allowed to be set without your permission. All other cookies need to be approved before they can be set in the browser.
You can change your consent to cookie usage at any time on our Privacy Policy page.