Adenovirus-mediated expression of pex, a noncatalytic fragment of matrix metalloproteinase-2, and it’s inhibition on angiogenesis and tumor growth
详细信息 查看全文
- 作者：Jin-ping Li (1)
Ying Hu (1)
Zhong-xiang Lin (1)
Zhi-qian Zhang (1) - 关键词：MMP ; 2 ; PEX ; CAM ; Angiogenesis ; Tumor growth ; R73 ; 3
- 刊名：Chinese Journal of Cancer Research
- 出版年：2006
- 出版时间：March 2006
- 年：2006
- 卷：18
- 期：1
- 页码：12-18
- 全文大小：468KB
- 参考文献：1. Risau W. Mechanisms of angiogenesis [J]. Nature (London) 1997; 386:671-. CrossRef
2. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease [J]. Nat Med 1995; 1: 27-1. CrossRef
3. Veikkola T, Karkkainen M, Claesson-Welsh L, et al. Regulation of angiogenesis via vascular endothelial growth factor receptors [J]. Cancer Res 2000; 60:203-2.
4. O’Reilly, MS, Holmgren L, Shing Y, et al. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma [J]. Cell 1994; 79:315-8. CrossRef
5. O’Reilly MS, Boehm T, Shing Y, et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth [J]. Cell 1997; 88:277-5. CrossRef
6. Homandberg GA, Williams JE, Grant D, et al. Heparin-binding fragments of fibronectin are potent inhibitors of endothelial cell growth [J]. Am J Pathol 1985; 120:327-2.
7. Ferrara N, Clapp C, Weiner R. The 16K fragment of prolactin specifically inhibits basal or fibroblast growth factor stimulated growth of capillary endothelial cells [J]. Endocrinology 1991; 129:896-00. CrossRef
8. Brooks PC, Stromblad S, Sanders LC, et al. Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin α v β3 [J]. Cell 1996; 85:683-3. CrossRef
9. Brooks PC, Silletti S, von Schalscha TL, et al. Disruption of angogenesis by PEX, a noncatalytic metalloproteinase fragment with integrin binding activity [J]. Cell 1998; 92:391-00. CrossRef
10. Pfeifer A, Kessler T, Silletti S, et al. Suppression of angiogenesis by lentiviral delivery of PEX, a noncatalytic fragment of matrix metalloproteinase 2 [J]. Proc Natl Acad Sci USA 2000; 97:12227-2. CrossRef
11. Silletti S, Cheresch DA. A link between integrins and MMPs in angiogenesis [J]. Fibrinolysis Proteinolysis 1999; 13:226-8. CrossRef
12. Lyden D, Young AZ, Zagzag D, et al. Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts [J]. Nature 1999; 401:670-. CrossRef
13. Chen WT, Wang JY. Specialized surface protrusions of invasive cells, invadopodia and lamellipodis, have differential MT1-MMP, MMP-2, and TIMP-2 localization [J]. Ann N Y Acad Sci 1999; 878:361-1. CrossRef
14. Hofmann UB, Westphal JR, Van Kraats AA, et al. Expression of integrin alpha (v) beta (3) correlates with activation of membrane type matrix metalloproteinase-1 (MT1-MMP) and matrix metalloproteinase-2 (MMP-2) in human melanoma cells in vitro and in vivo [J]. Int J Cancer 2000; 87:12-. CrossRef - 作者单位：Jin-ping Li (1)
Ying Hu (1)
Zhong-xiang Lin (1)
Zhi-qian Zhang (1)
1. Department of Cell Biology, Beijing Institute for Cancer Research, Peking University School of Oncology, Beijing, 100036, China
文摘
Objective To develop an adenovirus system to deliver biologically active peptides or proteins such as angiogenesis inhibitors in vivo for the treatment of cancer. Methods DNA recombination techniques were employed to construct adenovirus shuttle vector, in which angiogenesis inhibitor was put downstream of rat growth hormone signal peptide, and the C-terminal was the myc-epitope 10-amino-acid peptide for the following up of the protein. Adenovirus was made using the bacteria recombination method. We tested this system using an angiogenesis inhibitor chick MMP-2 C-terminal hemopexin-like fragment (PEX) in Sarcoma 180 (S-180) bearing Kunming mice. The anti-angiogenic effect was performed by chick chorioallantoic membrane assay. Results PEX was readily secreted outside human stomach carcinoma BGC823 cells as demonstrated by immunofluorescent staining and western blot infected by adenovirus with rat growth hormone signal peptide (E-T-rGH-PEX). However, without signal peptide (E-T-PEX), PEX was expressed and localized in the cytoplasm of the infected cells, and formed large aggregates, which suggested that PEX was insoluble. The adenovirus E-T-rGH-PEX could inhibit angiogenesis, while E-T-rGH-PEX not. The adenoviruses of E-T-rGH-PEX inhibited the growth of S-180 tumor significantly compared with the empty virus control group E-T (P=0.026) and without signal peptide group E-T-PEX (P=0.006) respectively, while E-T-PEX had little effect. Conclusion These results suggest that this adenoviral system is likely to be used in the gene therapy of cancer to deliver angiogenesis inhibitors.