Multifaceted Roles of Asporin in Cancer: Current Understanding.
Journal: 2019/October - Frontiers in Oncology
ISSN: 2234-943X
Abstract:
The small leucine-rich proteoglycan (SLRP) family consists of 18 members categorized into five distinct classes, the traditional classes I-III, and the non-canonical classes IV-V. Unlike the other class I SLRPs (decorin and biglycan), asporin contains a unique and conserved stretch of aspartate (D) residues in its N terminus, and germline polymorphisms in the D-repeat-length are associated with osteoarthritis and prostate cancer progression. Since the first discovery of asporin in 2001, previous studies have focused mainly on its roles in bone and joint diseases, including osteoarthritis, intervertebral disc degeneration and periodontal ligament mineralization. Recently, asporin gene expression was also reported to be dysregulated in tumor tissues of different types of cancer, and to act as oncogene in pancreatic, colorectal, gastric, and prostate cancers, and some types of breast cancer, though it is also reported to function as a tumor suppressor gene in triple-negative breast cancer. Furthermore, asporin is also positively or negatively correlated with tumor proliferation, migration, invasion, and patient prognosis through its regulation of different signaling pathways, including the TGF-β, EGFR, and CD44 pathways. In this review, we seek to elucidate the signaling pathways and functions regulated by asporin in different types of cancer and to highlight some important issues that require investigation in future research.
Relations:
Content
Citations
(3)
References
(77)
Diseases
(3)
Drugs
(3)
Chemicals
(2)
Genes
(5)
Processes
(1)
Anatomy
(4)
Similar articles
Articles by the same authors
Discussion board
Front Oncol 9: 948

Multifaceted Roles of Asporin in Cancer: Current Understanding

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

National Key Laboratory of Medical Molecular Biology, Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China
National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Beijing, China
Affiliated Hospital of Hebei University, Baoding, China
Edited by: Satyendra Chandra Tripathi, All India Institute of Medical Sciences Nagpur, India
Reviewed by: Giuseppe Palma, National Cancer Institute G. Pascale Foundation (IRCCS), Italy; Prasanna Ekambaram, University of Pittsburgh, United States; Chandra Prakash Prasad, All India Institute of Medical Sciences, India
*Correspondence: Jinming Li nc.gro.lccn@ilmj
Wei Ge ku.ca.xo.mehc@eg.iew
This article was submitted to Molecular and Cellular Oncology, a section of the journal Frontiers in Oncology
Edited by: Satyendra Chandra Tripathi, All India Institute of Medical Sciences Nagpur, India
Reviewed by: Giuseppe Palma, National Cancer Institute G. Pascale Foundation (IRCCS), Italy; Prasanna Ekambaram, University of Pittsburgh, United States; Chandra Prakash Prasad, All India Institute of Medical Sciences, India
Received 2019 Jul 8; Accepted 2019 Sep 9.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Abstract

The small leucine-rich proteoglycan (SLRP) family consists of 18 members categorized into five distinct classes, the traditional classes I–III, and the non-canonical classes IV–V. Unlike the other class I SLRPs (decorin and biglycan), asporin contains a unique and conserved stretch of aspartate (D) residues in its N terminus, and germline polymorphisms in the D-repeat-length are associated with osteoarthritis and prostate cancer progression. Since the first discovery of asporin in 2001, previous studies have focused mainly on its roles in bone and joint diseases, including osteoarthritis, intervertebral disc degeneration and periodontal ligament mineralization. Recently, asporin gene expression was also reported to be dysregulated in tumor tissues of different types of cancer, and to act as oncogene in pancreatic, colorectal, gastric, and prostate cancers, and some types of breast cancer, though it is also reported to function as a tumor suppressor gene in triple-negative breast cancer. Furthermore, asporin is also positively or negatively correlated with tumor proliferation, migration, invasion, and patient prognosis through its regulation of different signaling pathways, including the TGF-β, EGFR, and CD44 pathways. In this review, we seek to elucidate the signaling pathways and functions regulated by asporin in different types of cancer and to highlight some important issues that require investigation in future research.

Keywords: SLRP, aspirin, cell migration and invasion, metastasis, signaling pathways
Abstract

Acknowledgments

We thank all lab members for active discussions and critical reading.

Acknowledgments

Footnotes

Funding. This work was supported by the CAMS Innovation Fund for Medical Sciences (2016-I2M-1-003), the National Natural Science Foundation of China (Nos. 81974319, 81772273, and 81971023), and the Beijing Municipal Administration of Hospitals' Youth Program (No. QML20161103).

Footnotes

References

  • 1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. (2018) 68:394–424. 10.3322/caac.21492 [] [[PubMed]
  • 2. Lu P, Weaver VM, Werb Z. The extracellular matrix: a dynamic niche in cancer progression. J Cell Biol. (2012) 196:395–406. 10.1083/jcb.201102147 ] [
  • 3. Pickup MW, Mouw JK, Weaver VM. The extracellular matrix modulates the hallmarks of cancer. EMBO Rep. (2014) 15:1243–53. 10.15252/embr.201439246 ] [
  • 4. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. (2000) 100:57–70. 10.1016/S0092-8674(00)81683-9 [] [[PubMed]
  • 5. Ni GX, Li Z, Zhou YZ. The role of small leucine-rich proteoglycans in osteoarthritis pathogenesis. Osteoarthr Cartil. (2014) 22:896–903. 10.1016/j.joca.2014.04.026 [] [[PubMed]
  • 6. Ameye L, Young MF. Mice deficient in small leucine-rich proteoglycans: novel in vivo models for osteoporosis, osteoarthritis, Ehlers-Danlos syndrome, muscular dystrophy, and corneal diseases. Glycobiology. (2002) 12:107r–16. 10.1093/glycob/cwf065 [] [[PubMed]
  • 7. Reed CC, Iozzo RV. The role of decorin in collagen fibrillogenesis and skin homeostasis. Glycoconj J. (2002) 19:249–55. 10.1023/A:1025383913444 [] [[PubMed]
  • 8. Nikitovic D, Berdiaki K, Chalkiadaki G, Karamanos N, Tzanakakis G. The role of SLRP-proteoglycans in osteosarcoma pathogenesis. Connect Tissue Res. (2008) 49:235–8. 10.1080/03008200802147589 [] [[PubMed]
  • 9. Iozzo RV. The biology of the small leucine-rich proteoglycans. Functional network of interactive proteins. J Biol Chem. (1999) 274:18843–6. 10.1074/jbc.274.27.18843 [] [[PubMed]
  • 10. Schaefer L, Iozzo RV. Biological functions of the small leucine-rich proteoglycans: from genetics to signal transduction. J Biol Chem. (2008) 283:21305–9. 10.1074/jbc.R800020200 ] [
  • 11. McEwan PA, Scott PG, Bishop PN, Bella J. Structural correlations in the family of small leucine-rich repeat proteins and proteoglycans. J Struct Biol. (2006) 155:294–305. 10.1016/j.jsb.2006.01.016 [] [[PubMed]
  • 12. Kizawa H, Kou I, Iida A, Sudo A, Miyamoto Y, Fukuda A, et al. . An aspartic acid repeat polymorphism in asporin inhibits chondrogenesis and increases susceptibility to osteoarthritis. Nat Genet. (2005) 37:138–44. 10.1038/ng1496 [] [[PubMed]
  • 13. Gallagher JT, Gasiunas N, Schor SL. Specific association of iduronic acid-rich dermatan sulphate with the extracellular matrix of human skin fibroblasts cultured on collagen gels. Biochem J. (1983) 215:107–16. 10.1042/bj2150107 ] [
  • 14. Schmidt G, Robenek H, Harrach B, Glossl J, Nolte V, Hormann H, et al. . Interaction of small dermatan sulfate proteoglycan from fibroblasts with fibronectin. J Cell Biol. (1987) 104:1683–91. 10.1083/jcb.104.6.1683 ] [
  • 15. Henry SP, Takanosu M, Boyd TC, Mayne PM, Eberspaecher H, Zhou W, et al. . Expression pattern and gene characterization of asporin. A newly discovered member of the leucine-rich repeat protein family. J Biol Chem. (2001) 276:12212–21. 10.1074/jbc.M011290200 [] [[PubMed]
  • 16. 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) 276:12201–11. 10.1074/jbc.M010932200 [] [[PubMed]
  • 17. Schaefer L, Iozzo RV. Small leucine-rich proteoglycans, at the crossroad of cancer growth and inflammation. Curr Opin Genet Develop. (2012) 22:56–7. 10.1016/j.gde.2011.12.002 [] [[PubMed]
  • 18. Appunni S, Anand V, Khandelwal M, Gupta N, Rubens M, Sharma A. Small leucine rich proteoglycans (decorin, biglycan and lumican) in cancer. Clin Chim Acta. (2019) 491:1–7. 10.1016/j.cca.2019.01.003 [] [[PubMed]
  • 19. Sun H, Wang X, Zhang Y, Che X, Liu Z, Zhang L, et al. . Biglycan enhances the ability of migration and invasion in endometrial cancer. Arch Gynecol Obstetr. (2016) 293:429–38. 10.1007/s00404-015-3844-5 [] [[PubMed]
  • 20. Zhu Y-H, Yang F, Zhang S-S, Zeng T-T, Xie X, Guan X-Y. High expression of biglycan is associated with poor prognosis in patients with esophageal squamous cell carcinoma. Int J Clin Exp Pathol. (2013) 6:2497–505.
  • 21. Yamada S, Murakami S, Matoba R, Ozawa Y, Yokokoji T, Nakahira Y, et al. . Expression profile of active genes in human periodontal ligament and isolation of PLAP-1, a novel SLRP family gene. Gene. (2001) 275:279–86. 10.1016/S0378-1119(01)00683-7 [] [[PubMed]
  • 22. Hurley PJ, Sundi D, Shinder B, Simons BW, Hughes RM, Miller RM, et al. . Germline variants in asporin vary by race, modulate the tumor microenvironment, and are differentially associated with metastatic prostate cancer. Clin Cancer Res. (2016) 22:448–58. 10.1158/1078-0432.CCR-15-0256 ] [
  • 23. Jiang Q, Shi D, Yi L, Ikegawa S, Wang Y, Nakamura T, et al. . 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) 51:1068–72. 10.1007/s10038-006-0065-6 [] [[PubMed]
  • 24. Atif U, Philip A, Aponte J, Woldu EM, Brady S, Kraus VB, et al. . Absence of association of asporin polymorphisms and osteoarthritis susceptibility in US Caucasians. Osteoarthr Cartil. (2008) 16:1174–7. 10.1016/j.joca.2008.03.007 ] [
  • 25. Rodriguez-Lopez J, Pombo-Suarez M, Liz M, Gomez-Reino JJ, Gonzalez A. Lack of association of a variable number of aspartic acid residues in the asporin gene with osteoarthritis susceptibility: case-control studies in Spanish Caucasians. Arthr Res Ther. (2006) 8:R55. 10.1186/ar1920 ] [
  • 26. Jazayeri R, Qoreishi M, Hoseinzadeh HR, Babanejad M, Bakhshi E, Najmabadi H, et al. . Investigation of the asporin gene polymorphism as a risk factor for knee osteoarthritis in Iran. Am J Orthop. (2013) 42:313–6. [[PubMed]
  • 27. Grimaud E, Heymann D, Redini F. Recent advances in TGF-beta effects on chondrocyte metabolism. Potential therapeutic roles of TGF-beta in cartilage disorders. Cytokine Growth Factor Rev. (2002) 13:241–57. 10.1016/S1359-6101(02)00004-7 [] [[PubMed]
  • 28. Kou I, Nakajima M, Ikegawa S. Binding characteristics of the osteoarthritis-associated protein asporin. J Bone Mineral Metab. (2010) 28:395–402. 10.1007/s00774-009-0145-8 [] [[PubMed]
  • 29. 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) 282:32185–92. 10.1074/jbc.M700522200 [] [[PubMed]
  • 30. Kou I, Nakajima M, Ikegawa S. Expression and regulation of the osteoarthritis-associated protein asporin. J Biol Chem. (2007) 282:32193–9. 10.1074/jbc.M706262200 [] [[PubMed]
  • 31. Liu Y, Hou R, Yin R, Yin W. Correlation of bone morphogenetic protein-2 levels in serum and synovial fluid with disease severity of knee osteoarthritis. Med Sci Monit. (2015) 21:363–70. 10.12659/MSM.892160 ] [
  • 32. van der Kraan PM, Blaney Davidson EN, van den Berg WB. Bone morphogenetic proteins and articular cartilage: to serve and protect or a wolf in sheep clothing's?Osteoarthr Cartil. (2010) 18:735–41. 10.1016/j.joca.2010.03.001 [] [[PubMed]
  • 33. Yamada S, Tomoeda M, Ozawa Y, Yoneda S, Terashima Y, Ikezawa K, et al. . PLAP-1/asporin, a novel negative regulator of periodontal ligament mineralization. J Biol Chem. (2007) 282:23070–80. 10.1074/jbc.M611181200 [] [[PubMed]
  • 34. Kajikawa T, Yamada S, Tauchi T, Awata T, Yamaba S, Fujihara C, et al. . Inhibitory effects of PLAP-1/asporin on periodontal ligament cells. J Dental Res. (2014) 93:400–5. 10.1177/0022034513520549 [] [[PubMed]
  • 35. Yamada S, Ozawa Y, Tomoeda M, Matoba R, Matsubara K, Murakami S. Regulation of PLAP-1 expression in periodontal ligament cells. J Dental Res. (2006) 85:447–51. 10.1177/154405910608500510 [] [[PubMed]
  • 36. Kalamajski S, Aspberg A, Lindblom K, Heinegard D, Oldberg A. Asporin competes with decorin for collagen binding, binds calcium and promotes osteoblast collagen mineralization. Biochem J. (2009) 423:53–9. 10.1042/BJ20090542 [] [[PubMed]
  • 37. Wang J, Yu H, Ye L, Jin L, Yu M, Lv Y. Integrated regulatory mechanisms of miRNAs and targeted genes involved in colorectal cancer. Int J Clin Exp Pathol. (2015) 8:517–29.
  • 38. Liu X, Wu J, Zhang D, Bing Z, Tian J, Ni M, et al. . Identification of potential key genes associated with the pathogenesis and prognosis of gastric cancer based on integrated bioinformatics analysis. Front. Genet. (2018) 9:265. 10.3389/fgene.2018.00265 ] [
  • 39. Jiang K, Liu H, Xie D, Xiao Q. Differentially expressed genes ASPN, COL1A1, FN1, VCAN and MUC5AC are potential prognostic biomarkers for gastric cancer. Oncol Lett. (2019) 17:3191–202. 10.3892/ol.2019.9952 ] [
  • 40. Turtoi A, Musmeci D, Wang Y, Dumont B, Somja J, Bevilacqua G, et al. . Identification of novel accessible proteins bearing diagnostic and therapeutic potential in human pancreatic ductal adenocarcinoma. J Proteome Res. (2011) 10:4302–13. 10.1021/pr200527z [] [[PubMed]
  • 41. Klee EW, Bondar OP, Goodmanson MK, Dyer RB, Erdogan S, Bergstralh EJ, et al. . 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) 58:599–609. 10.1373/clinchem.2011.171637 ] [
  • 42. Mackay A, Urruticoechea A, Dixon JM, Dexter T, Fenwick K, Ashworth A, et al. . Molecular response to aromatase inhibitor treatment in primary breast cancer. Breast Cancer Res. (2007) 9:R37. 10.1186/bcr1732 ] [
  • 43. Turashvili G, Bouchal J, Baumforth K, Wei W, Dziechciarkova M, Ehrmann J, et al. . Novel markers for differentiation of lobular and ductal invasive breast carcinomas by laser microdissection and microarray analysis. BMC Cancer. (2007) 7:55. 10.1186/1471-2407-7-55 ] [
  • 44. Wang L, Wu H, Wang L, Zhang H, Lu J, Liang Z, et al. . Asporin promotes pancreatic cancer cell invasion and migration by regulating the epithelial-to-mesenchymal transition (EMT) through both autocrine and paracrine mechanisms. Cancer Lett. (2017) 398:24–36. 10.1016/j.canlet.2017.04.001 [] [[PubMed]
  • 45. Li H, Zhang Z, Chen L, Sun X, Zhao Y, Guo Q, et al. . Cytoplasmic Asporin promotes cell migration by regulating TGF-beta/Smad2/3 pathway and indicates a poor prognosis in colorectal cancer. Cell Death Dis. (2019) 10:109. 10.1038/s41419-019-1376-9 ] [
  • 46. Huo WU, Jing X, Cheng X, He Y, Hu L, Wu H, et al Asporin enhances colorectal cancer metastasis through activating the EGFR/src/cortactin signaling pathway. Oncotarget. (2016) 7:73402–73413. 10.18632/oncotarget.12336 ] [[Google Scholar]
  • 47. Satoyoshi R, Kuriyama S, Aiba N, Yashiro M, Tanaka M. Asporin activates coordinated invasion of scirrhous gastric cancer and cancer-associated fibroblasts. Oncogene. (2015) 34:650–60. 10.1038/onc.2013.584 [] [[PubMed]
  • 48. Ding Q, Zhang M, Liu C. Asporin participates in gastric cancer cell growth and migration by influencing EGF receptor signaling. Oncol Rep. (2015) 33:1783–90. 10.3892/or.2015.3791 [] [[PubMed]
  • 49. Rochette A, Boufaied N, Scarlata E, Hamel L, Brimo F, Whitaker HC, et al. . Asporin is a stromally expressed marker associated with prostate cancer progression. Br J Cancer. (2017) 116:775. 10.1038/bjc.2017.15 ] [
  • 50. Castellana B, Escuin D, Peiro G, Garcia-Valdecasas B, Vazquez T, Pons C, et al. . ASPN and GJB2 are implicated in the mechanisms of invasion of ductal breast carcinomas. J Cancer. (2012) 3:175–83. 10.7150/jca.4120 ] [
  • 51. Simkova D, Kharaishvili G, Korinkova G, Ozdian T, Suchánková-Kleplová T, Soukup T, et al. . The dual role of asporin in breast cancer progression. Oncotarget. (2016) 7, 52045–52060. 10.18632/oncotarget.10471 ] [
  • 52. Maris P, Blomme A, Palacios AP, Costanza B, Bellahcène A, Bianchi E, et al. . Asporin is a fibroblast-derived TGF-β1 inhibitor and a tumor suppressor associated with good prognosis in breast cancer. PLoS Med. (2015) 12:e1001871. 10.1371/journal.pmed.1001871 ] [
  • 53. Derynck R, Akhurst RJ, Balmain A. TGF-beta signaling in tumor suppression and cancer progression. Nat Genet. (2001) 29:117–29. 10.1038/ng1001-117 [] [[PubMed]
  • 54. de Caestecker MP, Piek E, Roberts AB. Role of transforming growth factor-beta signaling in cancer. J Natl Cancer Inst. (2000) 92:1388–402. 10.1093/jnci/92.17.1388 [] [[PubMed]
  • 55. Zarzynska JM. Two faces of TGF-beta1 in breast cancer. Mediat Inflamm. (2014) 2014:141747. 10.1155/2014/141747 ] [
  • 56. Jung B, Staudacher JJ, Beauchamp D. Transforming growth factor beta superfamily signaling in development of colorectal cancer. Gastroenterology. (2017) 152:36–52. 10.1053/j.gastro.2016.10.015 ] [
  • 57. Wee P, Wang Z. Epidermal growth factor receptor cell proliferation signaling pathways. Cancers. (2017) 9:E52. 10.3390/cancers9050052 ] [
  • 58. Sigismund S, Avanzato D, Lanzetti L. Emerging functions of the EGFR in cancer. Mol Oncol. (2018) 12:3–20. 10.1002/1878-0261.12155 ] [
  • 59. Scaltriti M, Baselga J. The epidermal growth factor receptor pathway: a model for targeted therapy. Clin Cancer Res. (2006) 12:5268–72. 10.1158/1078-0432.CCR-05-1554 [] [[PubMed]
  • 60. Barnard JA, Beauchamp RD, Russell WE, Dubois RN, Coffey RJ. Epidermal growth factor-related peptides and their relevance to gastrointestinal pathophysiology. Gastroenterology. (1995) 108:564–80. 10.1016/0016-5085(95)90087-X [] [[PubMed]
  • 61. Zhang Z, Li H, Zhao Y, Guo Q, Yu Y, Zhu S, et al. . Asporin promotes cell proliferation via interacting with PSMD2 in gastric cancer. Front Biosci. (2019) 24:1178–89. 10.2741/4774 [] [[PubMed]
  • 62. Artym VV, Zhang Y, Seillier-Moiseiwitsch F, Yamada KM, Mueller SC. Dynamic interactions of cortactin and membrane type 1 matrix metalloproteinase at invadopodia: defining the stages of invadopodia formation and function. Cancer Res. (2006) 66:3034–43. 10.1158/0008-5472.CAN-05-2177 [] [[PubMed]
  • 63. Clark ES, Whigham AS, Yarbrough WG, Weaver AM. Cortactin is an essential regulator of matrix metalloproteinase secretion and extracellular matrix degradation in invadopodia. Cancer Res. (2007) 67:4227–35. 10.1158/0008-5472.CAN-06-3928 [] [[PubMed]
  • 64. Senbanjo LT, Chellaiah MA. CD44: a multifunctional cell surface adhesion receptor is a regulator of progression and metastasis of cancer cells. Front Cell Develop Biol. (2017) 5:18. 10.3389/fcell.2017.00018 ] [
  • 65. Ponta H, Sherman L, Herrlich PA. CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol. (2003) 4:33–45. 10.1038/nrm1004 [] [[PubMed]
  • 66. Chen C, Zhao S, Karnad A, Freeman JW. The biology and role of CD44 in cancer progression: therapeutic implications. J Hematol Oncol. (2018) 11:64. 10.1186/s13045-018-0605-5 ] [
  • 67. Hughes RM, Simons BW, Khan H, Miller R, Kugler V, Torquato S, et al. . Asporin restricts mesenchymal stromal cell differentiation, alters the tumor microenvironment, and drives metastatic progression. Cancer Res. (2019) 79:3636–50. 10.1158/0008-5472.CAN-18-2931 ] [
  • 68. Awata T, Yamada S, Tsushima K, Sakashita H, Yamaba S, Kajikawa T, et al. . PLAP-1/Asporin positively regulates FGF-2 activity. J Dental Res. (2015) 94:1417–24. 10.1177/0022034515598507 [] [[PubMed]
  • 69. Luehders K, Sasai N, Davaapil H, Kurosawa-Yoshida M, Hiura H, Brah T, et al. . The small leucine-rich repeat secreted protein Asporin induces eyes in Xenopus embryos through the IGF signalling pathway. Development. (2015) 142:3351–61. 10.1242/dev.124438 [] [[PubMed]
  • 70. Iozzo RV, Schaefer L. Proteoglycans in health and disease: novel regulatory signaling mechanisms evoked by the small leucine-rich proteoglycans. FEBS J. (2010) 277:3864–75. 10.1111/j.1742-4658.2010.07797.x ] [
  • 71. Ayala G, Tuxhorn JA, Wheeler TM, Frolov A, Scardino PT, Ohori M, et al. . Reactive stroma as a predictor of biochemical-free recurrence in prostate cancer. Clin Cancer Res. (2003) 9:4792–801. [[PubMed]
  • 72. Hsu PD, Lander ES, Zhang F. Development and applications of CRISPR-Cas9 for genome engineering. Cell. (2014) 157:1262–78. 10.1016/j.cell.2014.05.010 ] [
  • 73. Li C, Li C, Yue J, Huang X, Chen M, Gao J, et al. . miR-21 and miR-101 regulate PLAP-1 expression in periodontal ligament cells. Mol Med Rep. (2012) 5:1340–6. 10.3892/mmr.2012.797 [] [[PubMed]
  • 74. Rea D, Del Vecchio V, Palma G, Barbieri A, Falco M, Luciano A, et al. . Mouse models in prostate cancer translational research: from xenograft to PDX. Bio Med Res Int. (2016). 2016:9750795. 10.1155/2016/9750795 ] [
  • 75. Simkova D, Kharaishvili G, Slabakova E, Murray PG, Bouchal J. Glycoprotein asporin as a novel player in tumour microenvironment and cancer progression. Biomed Papers. (2016) 160:467–73. 10.5507/bp.2016.037 [] [[PubMed]
  • 76. Ikegawa S. Expression, regulation and function of asporin, a susceptibility gene in common bone and joint diseases. Curr Med Chem. (2008) 15:724–8. 10.2174/092986708783885237 [] [[PubMed]
  • 77. Xu L, Li Z, Liu S-Y, Xu S-Y, Ni G-X. Asporin and osteoarthritis. Osteoarthr Cartil. (2015) 23:933–9. 10.1016/j.joca.2015.02.011 [] [[PubMed]
Collaboration tool especially designed for Life Science professionals.Drag-and-drop any entity to your messages.