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The expression of tumstatin is down-regulated in renal carcinoma

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Abstract

Tumstatin is the 28 kDa NC1 domain of the α3 chain of type IV collagen that inhibits pathological angiogenesis and suppresses endothelial cell proliferation and tumor growth. In the present paper, we expressed and purified recombinant human tumstatin protein and then prepared the anti-tumstatin polyclonal antibody. To investigate the expression of tumstatin in renal carcinoma, tumstatin protein was detected by western blotting using the prepared anti-tumstatin antibody and tumstatin mRNA levels were assayed by RT-PCR. The results showed that the expression of tumstatin gene was down-regulated in renal carcinoma tissues and cells. Our study suggests that as a novel endogenous angiogenesis inhibitor, tumstatin gene expression may be a marker for diagnosis, therapy and prognosis of renal carcinoma.

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References

  1. Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid, and other disease. Nat Med 1:27–31

    Article  CAS  PubMed  Google Scholar 

  2. Folkman J, Shing Y (1992) Angiogenesis. J Biol Chem 267:10931–10934

    CAS  PubMed  Google Scholar 

  3. Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186

    CAS  PubMed  Google Scholar 

  4. O’Reilly MS, Boehm T, Shing Y, Fukai N, Vasios G, Lane WS, Flynn E, Birkhead JR, Olsen BR, Folkman J (1997) Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88:277–285

    Article  PubMed  Google Scholar 

  5. Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86:353–364

    Article  CAS  PubMed  Google Scholar 

  6. Hamano Y, Kalluri R (2005) Tumstatin, the NC1 domain of alpha3 chain of type IV collagen, is an endogenous inhibitor of pathological angiogenesis and suppresses tumor growth. Biochem Biophys Res Commun 333:292–298

    Article  CAS  PubMed  Google Scholar 

  7. Carmeliet P, Jain RK (2000) Angiogenesis in cancer and other diseases. Nature 407:249–257

    Article  CAS  PubMed  Google Scholar 

  8. Linguraru MG, Yao J, Gautam R, Peterson J, Li Z, Linehan WM, Summers RM (2009) Renal tumor quantification and classification in contrast-enhanced abdominal CT. Pattern Recognit 42:1149–1161

    Article  PubMed  Google Scholar 

  9. Carmeliet P (2005) Angiogenesis in life, disease and medicine. Nature 438:932–936

    Article  CAS  PubMed  Google Scholar 

  10. Carmeliet P (2005) VEGF as a key mediator of angiogenesis in cancer. Oncology 69:4–10

    Article  CAS  PubMed  Google Scholar 

  11. Yu J, Ustach C, Kim HR (2003) Platelet-derived growth factor signaling and human cancer. J Biochem Mol Biol 36:49–59

    CAS  PubMed  Google Scholar 

  12. Bochner BH, Cote RJ, Weidner N, Groshen S, Chen SC, Skinner DG, Nichols PW (1995) Angiogenesis in bladder cancer. Relationship between microvessel density and tumor prognosis. J Natl Cancer Inst 87:1603–1612

    Article  CAS  PubMed  Google Scholar 

  13. Giatromanolaki A, Koukourakis MI, Simopoulos C, Polychronidis A, Sivridis E (2003) Vascular endothelial growth factor (VEGF) expression in operable gallbladder carcinomas. Eur J Surgical Oncol 29:879–883

    Article  CAS  Google Scholar 

  14. Jacobsen J, Rasmuson T, Grankvist K, Ljunberg B (2000) Vascular endothelial growth factor as prognostic factor in renal cell carcinoma. J Urol 163:343–347

    Article  CAS  PubMed  Google Scholar 

  15. Maeshima Y, Colorado PC, Torre A, Holthaus KA, Grunkemeyer JA, Ericksen MB, Hopfer H, Xiao Y, Stillman IE, Kalluri R (2000) Distinct antitumor properties of a type IV collagen domain derived from basement membrane. J Biol Chem 275:21340–21348

    Article  CAS  PubMed  Google Scholar 

  16. Maeshima Y, Colorado PC, Kalluri R (2000) Two RGD-independent alpha vbeta 3 integrin binding sites on tumstatin regulate distinct anti-tumor properties. J Biol Chem 275:23745–23750

    Article  CAS  PubMed  Google Scholar 

  17. Frojdman K, Pelliniemi LJ, Virtanen I (1998) Differential distribution of type IV collagen chains in the developing rat testis and ovary. Differentiation 63:125–130

    CAS  PubMed  Google Scholar 

  18. Hamano Y, Zeisberg M, Sugimoto H, Lively JC, Maeshima Y, Yang C, Hynes RO, Werb Z, Sudhakar A, Kalluri R (2003) Physiological levels of tumstatin, a fragment of collagen IV alpha3 chain, are generated by MMP-9 proteolysis and suppress angiogenesis via alphaV beta3 integrin. Cancer Cell 3:589–601

    Article  CAS  PubMed  Google Scholar 

  19. Hudson BG, Reeders ST, Tryggvason K (1993) Type IV collagen: structure, gene organization, and role in human diseases. Molecular basis of Goodpasture and Alport syndromes and diffuse leiomyomatosis. J Biol Chem 268:26033–26036

    CAS  PubMed  Google Scholar 

  20. Kahsai TZ, Enders GC, Gunwar S, Brunmark C, Wieslander J, Kalluri R, Zhou J, Noelken ME, Hudson BG (1997) Seminiferous tubule basement membrane. Composition and organization of type IV collagen chains, and the linkage of α3 (IV) and α5 (IV) chains. J Biol Chem 272:17023–17032

    Article  CAS  PubMed  Google Scholar 

  21. Maeshima Y, Yerramalla UL, Dhanabal M, Holthaus KA, Barbashov S, Kharbanda S, Reimer C, Manfredi M, Dickerson WM, Kalluri R (2001) Extracellular Matrix-derived peptide binds to αvß3 integrin and inhibits angiogenesis. J Biol Chem 276:31959–31968

    Article  CAS  PubMed  Google Scholar 

  22. Sudhakar A, Sugimoto H, Yang C, Lively JC, Zeisberg M, Kalluri R (2003) Human tumstatin and human endostatin exhibit distinct antiangiogenic activities mediated by αvß3 and α5ß1 integrins. Proc Natl Acad Sci USA 100:4766–4771

    Article  CAS  PubMed  Google Scholar 

  23. Maeshima Y, Manfredi M, Reimer C, Holthaus KA, Hopfer H, Chandamuri BR, Kharbanda S, Kalluri R (2001) Identification of the anti-angiogenic site within vascular basement membrane derived tumstatin. J Biol Chem 276:15240–15248

    Article  CAS  PubMed  Google Scholar 

  24. Maeshima Y, Sudhakar A, Lively JC, Ueki K, Kharbanda S, Kahn CR, Sonenberg N, EHynes RO, Kalluri R (2002) Tumstatin, an endothelial cell-specific inhibitor of protein synthesis. Science 295:140–143

    Article  CAS  PubMed  Google Scholar 

  25. Pasco S, Ramont L, Venteo L, Pluot M, Maquart FX, Monboisse JC (2004) In vivo overexpression of tumstatin domains by tumor cells inhibits their invasive properties in a mouse melanoma model. Exp Cell Res 301:251–265

    Article  CAS  PubMed  Google Scholar 

  26. Chung IS, Son YI, Ko YJ, Baek CH, Cho JK, Jeong HS (2008) Peritumor injections of purified tumstatin delay tumor growth and lymphatic metastasis in an orthotopic oral squamous cell carcinoma model. Oral Oncology 44:1118–1126

    Article  CAS  PubMed  Google Scholar 

  27. Gu Q, Zhang T, Luo J, Wang F (2006) Expression, purification and bioactivity of human tumstatin from Escherichia coli. Protein Expr Purif 47:461–466

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We would like to thank Dr. Jifeng Bian for donation of pTriEx-4 plasmid and Dr. Yuzhu Xiang for collection of renal carcinoma and adjacent tissues. This work was supported by the Foundation of the Department of Science and Technology of Shandong Province (No: 2008GG30002030).

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Authors and Affiliations

  1. Institute of Biochemistry and Molecular Biology, School of Medicine, Shandong University, 44#, Wenhua Xi Road, 250012, Jinan, Shandong, China

    Chun-xiao Xu, Xian-xi Liu, Yun-fei Yan, Shi-min Chen, Wei Wang, Bin Liu & Jia-xuan Xin

  2. Quangang Pharmaceutical (SD) Co., Ltd., 250014, Jinan, China

    Guo-sheng Hou

  3. Hospital of Stomatology, Shandong University, 250012, Jinan, China

    Guang-shui Jiang

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  1. Chun-xiao Xu
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  2. Xian-xi Liu
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  3. Guo-sheng Hou
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  4. Yun-fei Yan
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  5. Shi-min Chen
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  6. Wei Wang
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  7. Guang-shui Jiang
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  8. Bin Liu
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  9. Jia-xuan Xin
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Correspondence to Xian-xi Liu.

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Xu, Cx., Liu, Xx., Hou, Gs. et al. The expression of tumstatin is down-regulated in renal carcinoma. Mol Biol Rep 37, 2273–2277 (2010). https://doi.org/10.1007/s11033-009-9718-9

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  • DOI: https://doi.org/10.1007/s11033-009-9718-9

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