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DCN deficiency promotes renal cell carcinoma growth and metastasis through downregulation of P21 and E-cadherin

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Tumor Biology

Abstract

Decorin (DCN), as an important component of the extracellular matrix (ECM), is a small leucine-rich proteoglycan and synthesized by fibroblasts. Although DCN is dysregulated in numerous cancer types, limited data are available on the expression level and important role of DCN proteins in renal cell carcinoma (RCC). In our study, we examined the expression patterns of DCN messenger RNA (mRNA) in RCCs through the Oncomine database and DCN protein in 94 RCC specimens by immunohistochemistry (IHC). The results revealed that DCN expression was decreased in cancerous tissues compared to adjacent noncancerous tissues and was highly correlated to tumor size. Then, via gain-of-function analyses, DCN overexpression could inhibit RCC cell proliferation and metastasis in vitro and vivo. At the mechanism level, we found that an ectopic expression of DCN significantly upregulated P21 and E-cadherin expression. Altogether, these results revealed that DCN is a tumor suppressor in RCC, and it could serve as a potential therapeutic target in patients with RCC.

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References

  1. Chow WH, Dong LM, Devesa SS. Epidemiology and risk factors for kidney cancer. Nature Rev Urol. 2010;7:245–57.

    Article  Google Scholar 

  2. Chow WH, Devesa SS, Warren JL, Fraumeni Jr JF. Rising incidence of renal cell cancer in the United States. JAMA. 1999;281:1628–31.

    Article  CAS  PubMed  Google Scholar 

  3. Janzen NK, Kim Hl Fau - Figlin RA, Figlin Ra Fau - Belldegrun AS, Belldegrun AS: Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease.

  4. Edge Sb Fau - Compton CC, Compton CC: The American joint committee on cancer: the 7th edition of the ajcc cancer staging manual and the future of tnm.

  5. Jones J, Libermann TA: Genomics of renal cell cancer: the biology behind and the therapy ahead.

  6. Ljungberg B, Hanbury Dc Fau - Kuczyk MA, Kuczyk Ma Fau - Merseburger AS, Merseburger As Fau - Mulders PFA, Mulders Pf Fau - Patard J-J, Patard Jj Fau - Sinescu IC, Sinescu IC: Renal cell carcinoma guideline.

  7. Shibue T, Weinberg RA: Metastatic colonization: settlement, adaptation and propagation of tumor cells in a foreign tissue environment.

  8. Joyce JA, Pollard JW: Microenvironmental regulation of metastasis.

  9. Gupta GP, Massague J: Cancer metastasis: building a framework.

  10. Horvath Z, Kovalszky I, Fullar A, Kiss K, Schaff Z, Iozzo RV, Baghy K: Decorin deficiency promotes hepatic carcinogenesis.

  11. Iozzo RV: The biology of the small leucine-rich proteoglycans. Functional network of interactive proteins.

  12. Iozzo RV: Matrix proteoglycans: From molecular design to cellular function.

  13. Sofeu Feugaing DD, Gotte M Fau - Viola M, Viola M: More than matrix: The multifaceted role of decorin in cancer.

  14. Campioni M, Ambrogi V Fau - Pompeo E, Pompeo E Fau - Citro G, Citro G Fau - Castelli M, Castelli M Fau - Spugnini EP, Spugnini Ep Fau - Gatti A, Gatti A Fau - Cardelli P, Cardelli P Fau - Lorenzon L, Lorenzon L Fau - Baldi A, Baldi A Fau - Mineo TC, Mineo TC: Identification of genes down-regulated during lung cancer progression: a cdna array study.

  15. Iozzo RV, Cohen I: Altered proteoglycan gene expression and the tumor stroma.

  16. Mauviel A, Santra M Fau - Chen YQ, Chen Yq Fau - Uitto J, Uitto J Fau - Iozzo RV, Iozzo RV: Transcriptional regulation of decorin gene expression. Induction by quiescence and repression by tumor necrosis factor-alpha.

  17. Asundi VK, Dreher KL: Molecular characterization of vascular smooth muscle decorin: deduced core protein structure and regulation of gene expression.

  18. Yusenko MV, Kuiper Rp Fau - Boethe T, Boethe T Fau - Ljungberg B, Ljungberg B Fau - van Kessel AG, van Kessel Ag Fau - Kovacs G, Kovacs G: High-resolution DNA copy number and gene expression analyses distinguish chromophobe renal cell carcinomas and renal oncocytomas.

  19. Gumz ML, Zou H Fau - Kreinest PA, Kreinest Pa Fau - Childs AC, Childs Ac Fau - Belmonte LS, Belmonte Ls Fau - LeGrand SN, LeGrand Sn Fau - Wu KJ, Wu Kj Fau - Luxon BA, Luxon Ba Fau - Sinha M, Sinha M Fau - Parker AS, Parker As Fau - Sun LZ, Sun Lz Fau - Ahlquist DA, Ahlquist Da Fau - Wood CG, Wood Cg Fau - Copland JA, Copland JA: Secreted frizzled-related protein 1 loss contributes to tumor phenotype of clear cell renal cell carcinoma.

  20. Lenburg ME, Liou Ls Fau - Gerry NP, Gerry Np Fau - Frampton GM, Frampton Gm Fau - Cohen HT, Cohen Ht Fau - Christman MF, Christman MF: Previously unidentified changes in renal cell carcinoma gene expression identified by parametric analysis of microarray data.

  21. Jones J, Otu H Fau - Spentzos D, Spentzos D Fau - Kolia S, Kolia S Fau - Inan M, Inan M Fau - Beecken WD, Beecken Wd Fau - Fellbaum C, Fellbaum C Fau - Gu X, Gu X Fau - Joseph M, Joseph M Fau - Pantuck AJ, Pantuck Aj Fau - Jonas D, Jonas D Fau - Libermann TA, Libermann TA: Gene signatures of progression and metastasis in renal cell cancer.

  22. Rhodes DR, Kalyana-Sundaram S Fau - Mahavisno V, Mahavisno V Fau - Varambally R, Varambally R Fau - Yu J, Yu J Fau - Briggs BB, Briggs Bb Fau - Barrette TR, Barrette Tr Fau - Anstet MJ, Anstet Mj Fau - Kincead-Beal C, Kincead-Beal C Fau - Kulkarni P, Kulkarni P Fau - Varambally S, Varambally S Fau - Ghosh D, Ghosh D Fau - Chinnaiyan AM, Chinnaiyan AM: Oncomine 3.0: Genes, pathways, and networks in a collection of 18,000 cancer gene expression profiles.

  23. Wei C, Wang X Fau - Chen M, Chen M Fau - Ouyang K, Ouyang K Fau - Song L-S, Song Ls Fau - Cheng H, Cheng H: Calcium flickers steer cell migration.

  24. Qian Q, Shi X, Lei Z, Zhan L, Liu RY, Zhao J, Yang B, Liu Z, Zhang HT: Methylated +58cpg site decreases dcn mrna expression and enhances tgf-beta/smad signaling in nsclc cells with high metastatic potential.

  25. Shintani K, Matsumine A Fau - Kusuzaki K, Kusuzaki K Fau - Morikawa J, Morikawa J Fau - Matsubara T, Matsubara T Fau - Wakabayashi T, Wakabayashi T Fau - Araki K, Araki K Fau - Satonaka H, Satonaka H Fau - Wakabayashi H, Wakabayashi H Fau - Iino T, Iino T Fau - Uchida A, Uchida A: Decorin suppresses lung metastases of murine osteosarcoma.

  26. Goldoni S, Seidler Dg Fau - Heath J, Heath J Fau - Fassan M, Fassan M Fau - Baffa R, Baffa R Fau - Thakur ML, Thakur Ml Fau - Owens RT, Owens Rt Fau - McQuillan DJ, McQuillan Dj Fau - Iozzo RV, Iozzo RV: An antimetastatic role for decorin in breast cancer.

  27. Stander M, Naumann U Fau - Dumitrescu L, Dumitrescu L Fau - Heneka M, Heneka M Fau - Loschmann P, Loschmann P Fau - Gulbins E, Gulbins E Fau - Dichgans J, Dichgans J Fau - Weller M, Weller M: Decorin gene transfer-mediated suppression of tgf-beta synthesis abrogates experimental malignant glioma growth in vivo.

  28. Mahmoud M, Upton Pd Fau - Arthur HM, Arthur HM: Angiogenesis regulation by tgfbeta signalling: Clues from an inherited vascular disease.

  29. Csordas G, Santra M Fau - Reed CC, Reed Cc Fau - Eichstetter I, Eichstetter I Fau - McQuillan DJ, McQuillan Dj Fau - Gross D, Gross D Fau - Nugent MA, Nugent Ma Fau - Hajnoczky G, Hajnoczky G Fau - Iozzo RV, Iozzo RV: Sustained down-regulation of the epidermal growth factor receptor by decorin. A mechanism for controlling tumor growth in vivo.

  30. Schonherr E, Sunderkotter C Fau - Iozzo RV, Iozzo Rv Fau - Schaefer L, Schaefer L: Decorin, a novel player in the insulin-like growth factor system.

  31. Shibata T, Hirohashi S: E-cadherin cell adhesion system in human cancer.

  32. Zhu JX, Goldoni S Fau - Bix G, Bix G Fau - Owens RT, Owens Rt Fau - McQuillan DJ, McQuillan Dj Fau - Reed CC, Reed Cc Fau - Iozzo RV, Iozzo RV: Decorin evokes protracted internalization and degradation of the epidermal growth factor receptor via caveolar endocytosis.

  33. Carlson E, Liu C, Chikama T, Hayashi Y, Kao C, Birk D, et al. Keratocan, a cornea-specific keratan sulfate proteoglycan, is regulated by lumican. J Biol Chem. 2005;280:25541–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Tran K, Griffith L, Wells A. Extracellular matrix signaling through growth factor receptors during wound healing. Wound Repair Regen. 2004;12:262–8.

    Article  PubMed  Google Scholar 

  35. Swindle C, Tran K, Johnson T, Banerjee P, Mayes A, Griffith L, et al. Epidermal growth factor (egf)-like repeats of human tenascin-c as ligands for egf receptor. J Cell Biol. 2001;154:459–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Santra M, Reed Cc Fau - Iozzo RV, Iozzo RV: Decorin binds to a narrow region of the epidermal growth factor (egf) receptor, partially overlapping but distinct from the egf-binding epitope.

  37. Santra M, Eichstetter I Fau - Iozzo RV, Iozzo RV: An anti-oncogenic role for decorin. Down-regulation of erbb2 leads to growth suppression and cytodifferentiation of mammary carcinoma cells.

  38. Patel S, Santra M Fau - McQuillan DJ, McQuillan Dj Fau - Iozzo RV, Iozzo Rv Fau - Thomas AP, Thomas AP: Decorin activates the epidermal growth factor receptor and elevates cytosolic ca2+ in a431 carcinoma cells.

  39. Gotte M, Greve B Fau - Kelsch R, Kelsch R Fau - Muller-Uthoff H, Muller-Uthoff H Fau - Weiss K, Weiss K Fau - Kharabi Masouleh B, Kharabi Masouleh B Fau - Sibrowski W, Sibrowski W Fau - Kiesel L, Kiesel L Fau - Buchweitz O, Buchweitz O: The adult stem cell marker musashi-1 modulates endometrial carcinoma cell cycle progression and apoptosis via notch-1 and P21waf1/cip1.

  40. Bi X, Tong C Fau - Dockendorff A, Dockendorff A Fau - Bancroft L, Bancroft L Fau - Gallagher L, Gallagher L Fau - Guzman G, Guzman G Fau - Iozzo RV, Iozzo Rv Fau - Augenlicht LH, Augenlicht Lh Fau - Yang W, Yang W: Genetic deficiency of decorin causes intestinal tumor formation through disruption of intestinal cell maturation.

  41. Buraschi S, Pal N Fau - Tyler-Rubinstein N, Tyler-Rubinstein N Fau - Owens RT, Owens Rt Fau - Neill T, Neill T Fau - Iozzo RV, Iozzo RV: Decorin antagonizes met receptor activity and down-regulates {beta}-catenin and myc levels.

  42. Goldoni S, Humphries A Fau - Nystrom A, Nystrom A Fau - Sattar S, Sattar S Fau - Owens RT, Owens Rt Fau - McQuillan DJ, McQuillan Dj Fau - Ireton K, Ireton K Fau - Iozzo RV, Iozzo RV: Decorin is a novel antagonistic ligand of the met receptor.

  43. Bi X, Pohl Nm Fau - Qian Z, Qian Z Fau - Yang GR, Yang Gr Fau - Gou Y, Gou Y Fau - Guzman G, Guzman G Fau - Kajdacsy-Balla A, Kajdacsy-Balla A Fau - Iozzo RV, Iozzo Rv Fau - Yang W, Yang W: Decorin-mediated inhibition of colorectal cancer growth and migration is associated with E-cadherin in vitro and in mice.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 81171391 and No. 81372743). We apologize to all the researchers whose relevant contributions were not cited due to space limitations.

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Correspondence to Xiaojun Zhou.

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The study protocol was approved by the Institutional Review Board of Nanjing University, and all of the participants signed an informed consent form.

The tests on animals were conducted according to Institutional Animal Care and User guidelines and experimental procedures were approved by the Model Animal Research Center of Jingling Hospital.

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Xu, Y., Xia, Q., Rao, Q. et al. DCN deficiency promotes renal cell carcinoma growth and metastasis through downregulation of P21 and E-cadherin. Tumor Biol. 37, 5171–5183 (2016). https://doi.org/10.1007/s13277-015-4160-1

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