The expression of tumstatin is down-regulated in renal carcinoma

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.

[1]  William Arbuthnot Sir Lane,et al.  Endostatin: An Endogenous Inhibitor of Angiogenesis and Tumor Growth , 1997, Cell.

[2]  Raghu Kalluri,et al.  Human tumstatin and human endostatin exhibit distinct antiangiogenic activities mediated by αvβ3 and α5β1 integrins , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[3]  Peter Carmeliet,et al.  VEGF as a Key Mediator of Angiogenesis in Cancer , 2005, Oncology.

[4]  Peter Carmeliet,et al.  Angiogenesis in life, disease and medicine , 2005, Nature.

[5]  R. Kalluri,et al.  Seminiferous Tubule Basement Membrane , 1997, The Journal of Biological Chemistry.

[6]  C. Kahn,et al.  Tumstatin, an Endothelial Cell-Specific Inhibitor of Protein Synthesis , 2002, Science.

[7]  P. Carmeliet,et al.  Angiogenesis in cancer and other diseases , 2000, Nature.

[8]  J. Folkman Angiogenesis in cancer, vascular, rheumatoid and other disease , 1995, Nature Medicine.

[9]  R. Kalluri,et al.  Extracellular matrix-derived peptide binds to alpha(v)beta(3) integrin and inhibits angiogenesis. , 2001, The Journal of biological chemistry.

[10]  I. Chung,et al.  Peritumor injections of purified tumstatin delay tumor growth and lymphatic metastasis in an orthotopic oral squamous cell carcinoma model. , 2008, Oral oncology.

[11]  R. Kalluri,et al.  Tumstatin, the NC1 domain of alpha3 chain of type IV collagen, is an endogenous inhibitor of pathological angiogenesis and suppresses tumor growth. , 2005, Biochemical and biophysical research communications.

[12]  L. Ventéo,et al.  In vivo overexpression of tumstatin domains by tumor cells inhibits their invasive properties in a mouse melanoma model. , 2004, Experimental cell research.

[13]  R. Hynes,et al.  Physiological levels of tumstatin, a fragment of collagen IV alpha3 chain, are generated by MMP-9 proteolysis and suppress angiogenesis via alphaV beta3 integrin. , 2003, Cancer cell.

[14]  Qu-liang Gu,et al.  Expression, purification, and bioactivity of human tumstatin from Escherichia coli. , 2006, Protein expression and purification.

[15]  R. Hynes,et al.  Physiological levels of tumstatin, a fragment of collagen IV alpha3 chain, are generated by MMP-9 proteolysis and suppress angiogenesis via alphaV beta3 integrin. , 2003, Cancer cell.

[16]  R. Kalluri,et al.  Two RGD-independent alpha vbeta 3 integrin binding sites on tumstatin regulate distinct anti-tumor properties. , 2000, The Journal of biological chemistry.

[17]  J. Folkman Tumor angiogenesis: therapeutic implications. , 1971, The New England journal of medicine.

[18]  S. Groshen,et al.  Angiogenesis in bladder cancer: relationship between microvessel density and tumor prognosis. , 1995, Journal of the National Cancer Institute.

[19]  R. Kalluri,et al.  Two RGD-independent αvβ3 Integrin Binding Sites on Tumstatin Regulate Distinct Anti-tumor Properties* , 2000, The Journal of Biological Chemistry.

[20]  R. Kalluri,et al.  Identification of the Anti-angiogenic Site within Vascular Basement Membrane-derived Tumstatin* , 2001, The Journal of Biological Chemistry.

[21]  L. Pelliniemi,et al.  Differential distribution of type IV collagen chains in the developing rat testis and ovary. , 1998, Differentiation; research in biological diversity.

[22]  R. Kalluri,et al.  Distinct Antitumor Properties of a Type IV Collagen Domain Derived from Basement Membrane* , 2000, The Journal of Biological Chemistry.

[23]  K. Grankvist,et al.  Vascular endothelial growth factor as prognostic factor in renal cell carcinoma. , 2000, The Journal of urology.

[24]  H. Kim,et al.  Platelet-derived growth factor signaling and human cancer. , 2003, Journal of biochemistry and molecular biology.

[25]  Ronald M. Summers,et al.  Renal tumor quantification and classification in contrast-enhanced abdominal CT , 2009, Pattern Recognit..

[26]  C. Simopoulos,et al.  Vascular endothelial growth factor (VEGF) expression in operable gallbladder carcinomas. , 2003, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[27]  K. Tryggvason,et al.  Type IV collagen: structure, gene organization, and role in human diseases. Molecular basis of Goodpasture and Alport syndromes and diffuse leiomyomatosis. , 1993, The Journal of biological chemistry.

[28]  J Folkman,et al.  Transplacental carcinogenesis by stilbestrol. , 1971, The New England journal of medicine.

[29]  D. Hanahan,et al.  Patterns and Emerging Mechanisms of the Angiogenic Switch during Tumorigenesis , 1996, Cell.