Biomedical papers, 2016 (vol. 160), issue 4

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2016, 160(4):467-473 | 10.5507/bp.2016.037

Glycoprotein asporin as a novel player in tumour microenvironment and cancer progression

Dana Simkovaa, Gvantsa Kharaishvilia, Eva Slabakovab, Paul G. Murrayc, Jan Bouchala
a Department of Clinical and Molecular Pathology and Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic
b Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Brno, Czech Republic
c Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK

Background: Small leucine rich proteoglycans (SLRPs), major non-collagen components of the extracellular matrix (ECM), have multiple biological roles with diverse effects. Asporin, a member of the SLRPs class I, competes with other molecules in binding to collagen and affects its mineralization. Its role in cancer is only now being elucidated.

Methods: The PubMed online database was used to search relevant reviews and original articles. Furthermore, altered asporin expression was analysed in publicly available genome-wide expression data at the Gene Expression Omnibus database.

Results: Polymorphisms in the N-terminal polyaspartate domain, which binds calcium, are associated with osteoarthritis and prostate cancer. Asporin also promotes the progression of scirrhous gastric cancer where it is required for coordinated invasion by cancer associated fibroblasts and cancer cells. Besides the enhanced expression of asporin observed in multiple cancer types, such as breast, prostate, gastric, pancreas and colon cancer, tumour suppressive effects of asporin were described in triple-negative breast cancer. We also discuss a number of factors modulating asporin expression in different cell types relevant for alterations toing the tumour microenvironment.

Conclusion: The apparent contradicting tumour promoting and suppressive effects of asporin require further investigation. Deciphering the role of asporin and other SLRPs in tumour-stroma interactions is needed for a better understanding of cancer progression and potentially also for novel tumour microenvironment based therapies.

Keywords: asporin, polymorphism, cancer, gastric, breast, prostate, adipose tissue, miRNAs

Received: May 4, 2016; Accepted: July 8, 2016; Prepublished online: September 5, 2016; Published: December 12, 2016


References

  1. Bosman FT, Stamenkovic I. Functional structure and composition of the extracellular matrix. J Pathol 2003;200(4):423-8. Go to original source... Go to PubMed...
  2. Kharaishvili G, Simkova D, Bouchalova K, Gachechiladze M, Narsia N, Bouchal J. The role of cancer-associated fibroblasts, solid stress and other microenvironmental factors in tumor progression and therapy resistance. Cancer Cell Int 2014;14:41. Go to original source... Go to PubMed...
  3. Jean C, Gravelle P, Fournie JJ, Laurent G. Influence of stress on extracellular matrix and integrin biology. Oncogene 2011;30(24):2697-706. Go to original source... Go to PubMed...
  4. Mecham RP. Overview of extracellular matrix. Curr Protoc Cell Biol 2001;Chapter 10:Unit 10.1. Go to original source... Go to PubMed...
  5. Schaefer L, Iozzo RV. Small leucine-rich proteoglycans, at the crossroad of cancer growth and inflammation. Curr Opin Genet Dev 2012;22(1):56-7.  Go to original source... Go to PubMed...
  6. Iozzo RV. Matrix proteoglycans: from molecular design to cellular function. Annu Rev Biochem 1998;67:609-52. Go to original source... Go to PubMed...
  7. Edwards IJ. Proteoglycans in prostate cancer. Nat Rev Urol 2012;9(4):196-206. Go to original source... Go to PubMed...
  8. Schaefer L, Schaefer RM. Proteoglycans: from structural compounds to signaling molecules. Cell Tissue Res 2010;339(1):237-46. Go to original source... Go to PubMed...
  9. Dellett M, Hu W, Papadaki V, Ohnuma S. Small leucine rich proteoglycan family regulates multiple signalling pathways in neural development and maintenance. Dev Growth Differ 2012;54(3):327-40. Go to original source... Go to PubMed...
  10. Xu L, Li Z, Liu SY, Xu SY, Ni GX. Asporin and osteoarthritis. Osteoarthritis Cartilage 2015;23(6):933-9. Go to original source... Go to PubMed...
  11. Ni GX, Li Z, Zhou YZ. The role of small leucine-rich proteoglycans in osteoarthritis pathogenesis. Osteoarthritis Cartilage 2014;22(7):896-903. Go to original source... Go to PubMed...
  12. Tian W, Zheng S, Jiang XZ, Wu CA, Wang N, Zhao DH. Asporin, a candidate protein for treatment of disc degenerative disease. Chin Med J (Engl) 2013;126(2):369-72. Go to PubMed...
  13. Ikegawa S. Expression, regulation and function of asporin, a susceptibility gene in common bone and joint diseases. Curr Med Chem 2008;15(7):724-8. Go to original source... Go to PubMed...
  14. Henry SP, Takanosu M, Boyd TC, Mayne PM, Eberspaecher H, Zhou W, de Crombrugghe B, Hook M, Mayne R. Expression pattern and gene characterization of asporin. a newly discovered member of the leucine-rich repeat protein family. J Biol Chem 2001;276(15):12212-21. Go to original source... Go to PubMed...
  15. Lorenzo P, Aspberg A, Onnerfjord P, Bayliss MT, Neame PJ, Heinegard D. Identification and characterization of asporin. a novel member of the leucine-rich repeat protein family closely related to decorin and biglycan. J Biol Chem 2001;276(15):12201-11. Go to original source... Go to PubMed...
  16. Yamada S, Murakami S, Matoba R, Ozawa Y, Yokokoji T, Nakahira Y, Ikezawa K, Takayama S, Matsubara K, Okada H. Expression profile of active genes in human periodontal ligament and isolation of PLAP-1, a novel SLRP family gene. Gene 2001;275(2):279-86. Go to original source... Go to PubMed...
  17. Kou I, Nakajima M, Ikegawa S. Binding characteristics of the osteoarthritis-associated protein asporin. J Bone Miner Metab 2010;28(4):395-402. Go to original source... Go to PubMed...
  18. Kizawa H, Kou I, Iida A, Sudo A, Miyamoto Y, Fukuda A, Mabuchi A, Kotani A, Kawakami A, Yamamoto S, Uchida A, Nakamura K, Notoya K, Nakamura Y, Ikegawa S. An aspartic acid repeat polymorphism in asporin inhibits chondrogenesis and increases susceptibility to osteoarthritis. Nat Genet 2005;37(2):138-44. Go to original source... Go to PubMed...
  19. Nakamura T, Shi D, Tzetis M, Rodriguez-Lopez J, Miyamoto Y, Tsezou A, Gonzalez A, Jiang Q, Kamatani N, Loughlin J, Ikegawa S. Meta-analysis of association between the ASPN D-repeat and osteoarthritis. Hum Mol Genet 2007;16(14):1676-81. Go to original source... Go to PubMed...
  20. Mustafa Z, Dowling B, Chapman K, Sinsheimer JS, Carr A, Loughlin J. Investigating the aspartic acid (D) repeat of asporin as a risk factor for osteoarthritis in a UK Caucasian population. Arthritis Rheum 2005;52(11):3502-6. Go to original source... Go to PubMed...
  21. Kaliakatsos M, Tzetis M, Kanavakis E, Fytili P, Chouliaras G, Karachalios T, Malizos K, Tsezou A. Asporin and knee osteoarthritis in patients of Greek origin. Osteoarthritis Cartilage 2006;14(6):609-11. Go to original source... Go to PubMed...
  22. Atif U, Philip A, Aponte J, Woldu EM, Brady S, Kraus VB, Jordan JM, Doherty M, Wilson AG, Moskowitz RW, Hochberg M, Loeser R, Renner JB, Chiano M. Absence of association of asporin polymorphisms and osteoarthritis susceptibility in US Caucasians. Osteoarthritis Cartilage 2008;16(10):1174-7. Go to original source... Go to PubMed...
  23. Valdes AM, Loughlin J, Oene MV, Chapman K, Surdulescu GL, Doherty M, Spector TD. Sex and ethnic differences in the association of ASPN, CALM1, COL2A1, COMP, and FRZB with genetic susceptibility to osteoarthritis of the knee. Arthritis Rheum 2007;56(1):137-46. Go to original source... Go to PubMed...
  24. Jiang Q, Shi D, Yi L, Ikegawa S, Wang Y, Nakamura T, Qiao D, Liu C, Dai J. Replication of the association of the aspartic acid repeat polymorphism in the asporin gene with knee-osteoarthritis susceptibility in Han Chinese. J Hum Genet 2006;51(12):1068-72. Go to original source... Go to PubMed...
  25. Shi D, Nakamura T, Dai J, Yi L, Qin J, Chen D, Xu Z, Wang Y, Ikegawa S, Jiang Q. Association of the aspartic acid-repeat polymorphism in the asporin gene with age at onset of knee osteoarthritis in Han Chinese population. J Hum Genet 2007;52(8):664-7. Go to original source... Go to PubMed...
  26. Liu D, Yang Q, Li M, Mu K, Zhang Y. Association of an asporin repeat polymorphism with ankylosing spondylitis in Han Chinese population: a case-control study. Clin Invest Med 2010;33(1):E63-8. Go to original source... Go to PubMed...
  27. Song YQ, Cheung KM, Ho DW, Poon SC, Chiba K, Kawaguchi Y, Hirose Y, Alini M, Grad S, Yee AF, Leong JC, Luk KD, Yip SP, Karppinen J, Cheah KS, Sham P, Ikegawa S, Chan D. Association of the asporin D14 allele with lumbar-disc degeneration in Asians. Am J Hum Genet 2008;82(3):744-7. Go to original source... Go to PubMed...
  28. Bijsterbosch J, Kloppenburg M, Reijnierse M, Rosendaal FR, Huizinga TW, Slagboom PE, Meulenbelt I. Association study of candidate genes for the progression of hand osteoarthritis. Osteoarthritis Cartilage 2013;21(4):565-9. Go to original source... Go to PubMed...
  29. Kalamajski S, Aspberg A, Lindblom K, Heinegård D, Oldberg A. Asporin competes with decorin for collagen binding, binds calcium and promotes osteoblast collagen mineralization. Biochem J 2009;423(1):53-9. Go to original source... Go to PubMed...
  30. Yamada S, Tomoeda M, Ozawa Y, Yoneda S, Terashima Y, Ikezawa K, Ikegawa S, Saito M, Toyosawa S, Murakami S. PLAP-1/asporin, a novel negative regulator of periodontal ligament mineralization. J Biol Chem 2007;282(32):23070-80. Go to original source... Go to PubMed...
  31. Lee EH, Park HJ, Jeong JH, Kim YJ, Cha DW, Kwon DK, Lee SH, Cho JY. The role of asporin in mineralization of human dental pulp stem cells J Cell Physiol. 2011;226(6):1676-82. Go to original source... Go to PubMed...
  32. Sakao K, Takahashi KA, Arai Y, Saito M, Honjyo K, Hiraoka N, Kishida T, Mazda O, Imanishi J, Kubo T. Asporin and transforming growth factor-beta gene expression in osteoblasts from subchondral bone and osteophytes in osteoarthritis. J Orthop Sci 2009;14(6):738-47. Go to original source... Go to PubMed...
  33. Dangaria SJ, Ito Y, Luan X, Diekwisch TG. Differentiation of neural-crest-derived intermediate pluripotent progenitors into committed periodontal populations involves unique molecular signature changes, cohort shifts, and epigenetic modifications. Stem Cells Dev 2011;20(1):39-52. Go to original source... Go to PubMed...
  34. Önnerfjord P, Khabut A, Reinholt FP, Svensson O, Heinegård D. Quantitative proteomic analysis of eight cartilaginous tissues reveals characteristic differences as well as similarities between subgroups. J Biol Chem 2012;287(23):18913-24. Go to original source... Go to PubMed...
  35. Kou I, Nakajima M, Ikegawa S. Expression and regulation of the osteoarthritis-associated protein asporin. J Biol Chem 2007;282(44):32193-9. Go to original source... Go to PubMed...
  36. Nakajima M, Kizawa H, Saitoh M, Kou I, Miyazono K, Ikegawa S. Mechanisms for asporin function and regulation in articular cartilage. J Biol Chem 2007;282(44):32185-92. Go to original source... Go to PubMed...
  37. Duval E, Bigot N, Hervieu M, Kou I, Leclercq S, Galéra P, Boumediene K, Baugé C. Asporin expression is highly regulated in human chondrocytes. Mol Med 2011;17(7-8):816-23. Go to original source... Go to PubMed...
  38. Tasheva ES, Klocke B, Conrad GW. Analysis of transcriptional regulation of the small leucine rich proteoglycans. Mol Vis 2004;10:758-72. Go to PubMed...
  39. Maris P, Blomme A, Palacios AP, Costanza B, Bellahcène A, Bianchi E, Gofflot S, Drion P, Trombino GE, Di Valentin E, Cusumano PG, Maweja S, Jerusalem G, Delvenne P, Lifrange E, Castronovo V, Turtoi A. Asporin Is a Fibroblast-Derived TGF-β1 Inhibitor and a Tumor Suppressor Associated with Good Prognosis in Breast Cancer. PLoS Med 2015;12(9):e1001871. Go to original source... Go to PubMed...
  40. Lee SD, Choi SY, Lim SW, Lamitina ST, Ho SN, Go WY, Kwon HM. TonEBP stimulates multiple cellular pathways for adaptation to hypertonic stress: organic osmolyte-dependent and -independent pathways. Am J Physiol Renal Physiol 2011;300(3):F707-15. Go to original source... Go to PubMed...
  41. Michl P, Ramjaun AR, Pardo OE, Warne PH, Wagner M, Poulsom R, D'Arrigo C, Ryder K, Menke A, Gress T, Downward J. CUTL1 is a target of TGF(beta) signaling that enhances cancer cell motility and invasiveness. Cancer Cell 2005;7(6):521-32. Go to original source... Go to PubMed...
  42. Schaeffer EM, Marchionni L, Huang Z, Simons B, Blackman A, Yu W, Parmigiani G, Berman DM. Androgen-induced programs for prostate epithelial growth and invasion arise in embryogenesis and are reactivated in cancer. Oncogene 2008;27(57):7180-91. Go to original source... Go to PubMed...
  43. Vaarala MH, Hirvikoski P, Kauppila S, Paavonen TK. Identification of androgen-regulated genes in human prostate. Mol Med Rep 2012;6(3):466-72. Go to original source... Go to PubMed...
  44. Mackay A, Urruticoechea A, Dixon JM, Dexter T, Fenwick K, Ashworth A, Drury S, Larionov A, Young O, White S, Miller WR, Evans DB, Dowsett M. Molecular response to aromatase inhibitor treatment in primary breast cancer. Breast Cancer Res 2007;9(3):R37. Go to original source... Go to PubMed...
  45. Slaby O, Svoboda M, Fabian P, Smerdova T, Knoflickova D, Bednarikova M, Nenutil R, Vyzula R. Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer. Oncology. 2007;72(5-6):397-402. Go to original source... Go to PubMed...
  46. Li C, Yue J, Huang X, Chen M, Gao J, Wu B. miR-21 and miR-101 regulate PLAP-1 expression in periodontal ligament cells. Mol Med Rep 2012;5(5):1340-6. Go to PubMed...
  47. Johnston IA, Lee HT, Macqueen DJ, Paranthaman K, Kawashima C, Anwar A, Kinghorn JR, Dalmay T. Embryonic temperature affects muscle fibre recruitment in adult zebrafish: genome-wide changes in gene and microRNA expression associated with the transition from hyperplastic to hypertrophic growth phenotypes. J Exp Biol 2009;212(Pt 12):1781-93. Go to original source... Go to PubMed...
  48. Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, Marshall KA, Phillippy KH, Sherman PM, Holko M, Yefanov A, Lee H, Zhang N, Robertson CL, Serova N, Davis S, Soboleva A. NCBI GEO: archive for functional genomics data sets--update. Nucleic Acids Res 2013;41(Database issue):D991-5.
  49. Vallender TW, Lahn BT. Localized methylation in the key regulator gene endothelin-1 is associated with cell type-specific transcriptional silencing. FEBS Lett 2006;580(18):4560-6. Go to original source... Go to PubMed...
  50. Wiesmann F, Veeck J, Galm O, Hartmann A, Esteller M, Knüchel R, Dahl E. Frequent loss of endothelin-3 (EDN3) expression due to epigenetic inactivation in human breast cancer. Breast Cancer Res 2009;11(3):R34 Go to original source... Go to PubMed...
  51. Ma XJ, Dahiya S, Richardson E, Erlander M, Sgroi DC. Gene expression profiling of the tumor microenvironment during breast cancer progression. Breast Cancer Res 2009;11(1):R7. Go to original source... Go to PubMed...
  52. Lim S, Metzger E, Schüle R, Kirfel J, Buettner R. Epigenetic regulation of cancer growth by histone demethylases. Int J Cancer 2010;127(9):1991-8. Go to original source... Go to PubMed...
  53. Turashvili G, Bouchal J, Baumforth K, Wei W, Dziechciarkova M, Ehrmann J, Klein J, Fridman E, Skarda J, Srovnal J, Hajduch M, Murray P, Kolar Z. Novel markers for differentiation of lobular and ductal invasive breast carcinomas by laser microdissection and microarray analysis. BMC Cancer 2007;7:55. Go to original source... Go to PubMed...
  54. Ma XJ, Wang Z, Ryan PD, Isakoff SJ, Barmettler A, Fuller A, Muir B, Mohapatra G, Salunga R, Tuggle JT, Tran Y, Tran D, Tassin A, Amon P, Wang W, Enright E, Stecker K, Estepa-Sabal E, Smith B, Younger J, Balis U, Michaelson J, Bhan A, Habin K, Baer TM, Brugge J, Haber DA, Erlander MG, Sgroi DC. A two-gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen. Cancer Cell 2004;5(6):607-16. Go to original source... Go to PubMed...
  55. Castellana B, Escuin D, Peiró G, Garcia-Valdecasas B, Vázquez T, Pons C, Pérez-Olabarria M, Barnadas A, Lerma E. ASPN and GJB2 Are Implicated in the Mechanisms of Invasion of Ductal Breast Carcinomas. J Cancer 2012;3:175-83. Go to original source... Go to PubMed...
  56. Klein A, Olendrowitz C, Schmutzler R, Hampl J, Schlag PM, Maass N, Arnold N, Wessel R, Ramser J, Meindl A, Scherneck S, Seitz S. Identification of brain- and bone-specific breast cancer metastasis genes. Cancer Lett 2009;276(2):212-20. Go to original source... Go to PubMed...
  57. Vona-Davis L, Rose DP, Gadiyaram V, Ducatman B, Hobbs G, Hazard H, Kurian S, Abraham J. Breast cancer pathology, receptor status, and patterns of metastasis in a rural appalachian population. J Cancer Epidemiol 2014;2014:170634. Go to original source... Go to PubMed...
  58. Creighton CJ, Li X, Landis M, Dixon JM, Neumeister VM, Sjolund A, Rimm DL, Wong H, Rodriguez A, Herschkowitz JI, Fan C, Zhang X, He X, Pavlick A, Gutierrez MC, Renshaw L, Larionov AA, Faratian D, Hilsenbeck SG, Perou CM, Lewis MT, Rosen JM, Chang JC. Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc Natl Acad Sci U S A 2009;106(33):13820-5. Go to original source... Go to PubMed...
  59. Martin-Padura I, Gregato G, Marighetti P, Mancuso P, Calleri A, Corsini C, Pruneri G, Manzotti M, Lohsiriwat V, Rietjens M, Petit JY, Bertolini F. The white adipose tissue used in lipotransfer procedures is a rich reservoir of CD34+ progenitors able to promote cancer progression. Cancer Res 2012;72(1):325-34. Go to original source... Go to PubMed...
  60. Kraman M, Bambrough PJ, Arnold JN, Roberts EW, Magiera L, Jones JO, Gopinathan A, Tuveson DA, Fearon DT. Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha. Science 2010;330(6005):827-30. Go to original source... Go to PubMed...
  61. Seale P, Kajimura S, Yang W, Chin S, Rohas LM, Uldry M, Tavernier G, Langin D, Spiegelman BM. Transcriptional control of brown fat determination by PRDM16. Cell Metab 2007;6(1):38-54. Go to original source... Go to PubMed...
  62. Yadav H, Quijano C, Kamaraju AK, Gavrilova O, Malek R, Chen W, Zerfas P, Zhigang D, Wright EC, Stuelten C, Sun P, Lonning S, Skarulis M, Sumner AE, Finkel T, Rane SG. Protection from obesity and diabetes by blockade of TGF-β/Smad3 signaling. Cell Metab 2011;14(1):67-79. Go to original source... Go to PubMed...
  63. Li D, Zhang Y, Xu L, Zhou L, Wang Y, Xue B, Wen Z, Li P, Sang J. Regulation of gene expression by FSP27 in white and brown adipose tissue. BMC Genomics 2010;11:446. Go to original source... Go to PubMed...
  64. Xu L, Xia X, Arshad M, Zhou L. Gene expression profile in the fat tissue of Fsp27 deficient mice. Genom Data 2015;5:326-8. Go to original source... Go to PubMed...
  65. Simkova D, Kharaishvili G, Korinkova G, Ozdian T, Suchankova-Kleplova T, Soukup T, Krupka M, Galandakova A, Dzubak P, Janikova M, Navratil J, Kahounova Z, Soucek K, Bouchal J. The dual role of asporin in breast cancer progression. Oncotarget 2016, accepted on 29th June 2016. doi: 10.18632/oncotarget.10471 Go to original source... Go to PubMed...
  66. Satoyoshi R, Kuriyama S, Aiba N, Yashiro M, Tanaka M. Asporin activates coordinated invasion of scirrhous gastric cancer and cancer-associated fibroblasts. Oncogene 2015; 34(5):650-60. Go to original source... Go to PubMed...
  67. Rajkumar T, Vijayalakshmi N, Gopal G, Sabitha K, Shirley S, Raja UM, Ramakrishnan SA. Identification and validation of genes involved in gastric tumorigenesis. Cancer Cell Int 2010;10:45. Go to original source... Go to PubMed...
  68. Ding Q, Zhang M, Liu C. Asporin participates in gastric cancer cell growth and migration by influencing EGF receptor signaling. Oncol Rep 2015;33(4):1783-90. Go to original source... Go to PubMed...
  69. Turtoi A, Musmeci D, Wang Y, Dumont B, Somja J, Bevilacqua G, De Pauw E, Delvenne P, Castronovo V. Identification of novel accessible proteins bearing diagnostic and therapeutic potential in human pancreatic ductal adenocarcinoma. J Proteome Res 2011;10 4302-13. Go to original source... Go to PubMed...
  70. Cima I, Schiess R, Wild P, Kaelin M, Schüffler P, Lange V, Picotti P, Ossola R, Templeton A, Schubert O, Fuchs T, Leippold T, Wyler S, Zehetner J, Jochum W, Buhmann J, Cerny T, Moch H, Gillessen S, Aebersold R, Krek W. Cancer genetics-guided discovery of serum biomarker signatures for diagnosis and prognosis of prostate cancer. Proc Natl Acad Sci U S A 2011;108:3342-7. Go to original source... Go to PubMed...
  71. Klee EW, Bondar OP, Goodmanson MK, Dyer RB, Erdogan S, Bergstralh EJ, Bergen HR, Sebo TJ, Klee GG. Candidate serum biomarkers for prostate adenocarcinoma identified by mRNA differences in prostate tissue and verified with protein measurements in tissue and blood. Clin Chem 2012;58(3):599-609. Go to original source... Go to PubMed...
  72. Best CJ, Gillespie JW, Yi Y, Chandramouli GV, Perlmutter MA, Gathright Y, Erickson HS, Georgevich L, Tangrea MA, Duray PH, González S, Velasco A, Linehan WM, Matusik RJ, Price DK, Figg WD, Emmert-Buck MR, Chuaqui RF. Molecular alterations in primary prostate cancer after androgen ablation therapy. Clin Cancer Res 2005;11(19 Pt 1):6823-34. Go to original source... Go to PubMed...
  73. Stanbrough M, Bubley GJ, Ross K, Golub TR, Rubin MA, Penning TM, Febbo PG, Balk SP. Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res 2006;66(5):2815-25. Go to original source... Go to PubMed...
  74. Hurley PJ, Sundi D, Shinder B, Simons BW, Hughes RM, Miller RM, Benzon B, Faraj SF, Netto GJ, Vergara IA, Erho N, Davicioni E, Karnes RJ, Yan G, Ewing C, Isaacs SD, Berman DM, Rider JR, Jordahl KM, Mucci LA, Huang J, An SS, Park BH, Isaacs WB, Marchionni L, Ross AE, Schaeffer EM. Germline Variants in Asporin Vary by Race, Modulate the Tumor Microenvironment, and Are Differentially Associated with Metastatic Prostate Cancer. Clin Cancer Res 2016;22(2):448-58. Go to original source... Go to PubMed...