Asporin Is a Fibroblast-Derived TGF-β1 Inhibitor and a Tumor Suppressor Associated with Good Prognosis in Breast Cancer

1. Juntilla MR, de Sauvage FJ. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature. 2013;501:346–354. doi: 10.1038/nature12626 24048067

2. Fiaschi T, Marini A, Giannoni E, Taddei ML, Gandellini P, De Donatis A, et al. Reciprocal metabolic reprogramming through lactate shuttle coordinately influences tumor-stroma interplay. Cancer Res. 2012;72:5130–5140. doi: 10.1158/0008-5472.CAN-12-1949 22850421

3. De Wever O, Van Bockstal M, Mareel M, Hendrix A, Bracke M. Carcinoma-associated fibroblasts provide operational flexibility in metastasis. Semin Cancer Biol. 2014;25C:33–46.

4. Dotto GP, Weinberg RA, Ariza A. Malignant transformation of mouse primary keratinocytes by Harvey sarcoma virus and its modulation by surrounding normal cells. Proc Natl Acad Sci U S A. 1988;85:6389–6393. 2457913

5. Shekhar MP, Werdell J, Santner SJ, Pauley RJ, Tait L. Breast stroma plays a dominant regulatory role in breast epithelial growth and differentiation: implications for tumor development and progression. Cancer Res. 2001;61:1320–1326. 11245428

6. Proia DA, Kuperwasser C. Stroma: tumor agonist or antagonist. Cell Cycle. 2005;4:1022–1025. 16082203

7. Mueller MM, Fusenig NE. Friends or foes—bipolar effects of the tumour stroma in cancer. Nat Rev Cancer. 2004;4:839–849. 15516957

8. Castronovo V, Waltregny D, Kischel P, Roesli C, Elia G, Rybak JN, et al. A chemical proteomics approach for the identification of accessible antigens expressed in human kidney cancer. Mol Cell Proteomics. 2006;5:2083–2091. 16861259

9. Conrotto P, Roesli C, Rybak J, Kischel P, Waltregny D, Neri D, et al. Identification of new accessible tumor antigens in human colon cancer by ex vivo protein biotinylation and comparative mass spectrometry analysis. Int J Cancer. 2008;123:2856–2864. doi: 10.1002/ijc.23861 18798264

10. 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;10:4302–4313. doi: 10.1021/pr200527z 21755970

11. Dumont B, Castronovo V, Peulen O, Blétard N, Clézardin P, Delvenne P, et al. Differential proteomic analysis of a human breast tumor and its matched bone metastasis identifies cell membrane and extracellular proteins associated with bone metastasis. J Proteome Res. 2012;11:2247–2260. doi: 10.1021/pr201022n 22356681

12. Merline R, Schaefer RM, Schaefer L. The matricellular functions of small leucine-rich proteoglycans (SLRPs). J Cell Commun Signal. 2009;3:323–335. doi: 10.1007/s12079-009-0066-2 19809894

13. 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;276:12201–12211. 11152692

14. Yamada S, Murakami S, Matoba R, Ozawa Y, Yokokoji T, Nakashira Y, et al. Expression profile of active genes in human periodontal ligament and isolation of PLAP-1, a novel SLRP family gene. Gene. 2001;275:279–286. 11587855

15. 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;37:138–144. 15640800

16. Orr B, Riddick AC, Stewart GD, Anderson RA, Franco OE, Hayward SW, et al. Identification of stromally expressed molecules in the prostate by tag-profiling of cancer-associated fibroblasts, normal fibroblasts and fetal prostate. Oncogene. 2012;31:1130–1142. doi: 10.1038/onc.2011.312 21804603

17. Satoyoshi R, Kuriyama S, Aiba N, Yashiro M, Tanaka M. Asporin activates coordinated invasion of scirrhous gastric cancer and cancer-associated fibroblasts. Oncogene. 2015;34:650–660. doi: 10.1038/onc.2013.584 24441039

18. Kou I, Nakajima M, Ikegawa S. Binding characteristics of the osteoarthritis-associated protein asporin. J Bone Miner Metab. 2010;28:395–402. doi: 10.1007/s00774-009-0145-8 20052601

19. de Visser KE, Kast WM. Effects of TGF-β on the immune system: implications for cancer immunotherapy. Leukemia. 1999;13:1188–1199. 10450746

20. Go C, Li P, Wang XJ. Blocking transforming growth factor-β signaling in transgenic epidermis accelerates chemical carcinogenesis: a mechanism associated with increased angiogenesis. Cancer Res. 1999;59:2861–2868. 10383147

21. Drabsch Y, ten Dijke P. TGF-β signaling in breast cancer cell invasion and bone metastasis. J Mammary Gland Biol. Neoplasia. 2011;16:97–108.

22. Han G, Lu SL, Li AG, He W, Corless CL, Kulesz-Martin M, et al. Distinct mechanisms of TGF-beta1-mediated epithelial-to-mesenchymal transition and metastasis during skin carcinogenesis. J Clin Invest. 2005;115:1714–1723. 15937546

23. Padua D, Zhang XH, Wang Q, Nadal C, Gerald WL, Gomis RR, et al. TGFbeta primes breast tumors for lung metastasis seeding through angiopoietin-like 4. Cell. 2008;133:66–77. doi: 10.1016/j.cell.2008.01.046 18394990

24. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133:704–715. doi: 10.1016/j.cell.2008.03.027 18485877

25. Tang B, Yoo N, Vu M, Mamura M, Nam JS, Ooshima A, et al. Transforming growth factor-beta can suppress tumorigenesis through effects on the putative cancer stem or early progenitor cells and committed progeny in a breast cancer xenograft model. Cancer Res. 2007;67:8643–8652. 17875704

26. Bierie B, Moses HL. Tumour microenvironment: TGFbeta: the molecular Jekyll and Hyde of cancer. Nat Rev Cancer. 2006;6:506–520. 16794634

27. Waltregny D, Bellahcène A, Van Riet I, Fisher LW, Young M, Fernandez P, et al. Prognostic value of bone sialoprotein expression in clinically localized human prostate cancer. J Natl Cancer Inst. 1998;90:1000–1008. 9665149

28. Daly AC, Vizán P, Hill CS. Smad3 protein levels are modulated by Ras activity and during the cell cycle to dictate transforming growth factor-beta responses. J Biol Chem. 2010;285:6489–6497. doi: 10.1074/jbc.M109.043877 20037158

29. Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010;8:e1000412. doi: 10.1371/journal.pbio.1000412 20613859

30. Lee RH, Pulin AA, Seo MJ, Kota DJ, Ylostalo J, Larson BL, et al. Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell. 2009;5:54–63. doi: 10.1016/j.stem.2009.05.003 19570514

31. Gyorffy B, Lanczky A, Eklund AC, Denkert C, Budczies J, Li Q, et al. An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1809 patients. Breast Cancer Res Treat. 2010;123:725–731. doi: 10.1007/s10549-009-0674-9 20020197

32. Ringnér M, Fredlund E, Häkkinen J, Borg Å, Staaf J. GOBO: gene expression-based outcome for breast cancer online. PLoS ONE 2011;6:e17911. doi: 10.1371/journal.pone.0017911 21445301

33. Sommers CL, Byers SW, Thompson EW, Torri JA, Gelmann EP. Differentiation state and invasiveness of human breast cancer cell lines. Breast Cancer Res Treat. 1994;31:325–335. 7881109

34. Minn AJ, Kang Y, Serganova I, Gupta GP, Giri DD, Doubrovin M, et al. Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors. J Clin Invest. 2005;115:44–55. 15630443

35. Neve RM, Chin K, Fridlyand J, Yeh J, Baehner FL, Fevr T, et al. A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell. 2006;10:515–527. 17157791

36. Bayer I, Groth P, Schneckener S. Prediction errors in learning drug response from gene expression data—influence of labeling, sample size, and machine learning algorithm. PLoS ONE. 2013;8:e70294. doi: 10.1371/journal.pone.0070294 23894636

37. David M, Sahay D, Mege F, Descotes F, Leblanc R, Ribeiro J, et al. Identification of heparin-binding EGF-like growth factor (HB-EGF) as a biomarker for lysophosphatidic acid receptor type 1 (LPA1) activation in human breast and prostate cancers. PLoS ONE. 2014;9:e97771. doi: 10.1371/journal.pone.0097771 24828490

38. Pinkas J, Leder P. MEK1 signaling mediates transformation and metastasis of EpH4 mammary epithelial cells independent of an epithelial to mesenchymal transition. Cancer Res. 2002;62:4781–4790. 12183438

39. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003;100:3983–3988. 12629218

40. Olsen CJ, Moreira J, Lukanidin EM, Ambartsumian NS. Human mammary fibroblasts stimulate invasion of breast cancer cells in a three-dimensional culture and increase stroma development in mouse xenografts. BMC Cancer. 2010;10:444. doi: 10.1186/1471-2407-10-444 20723242

41. Tyan SW, Kuo WH, Huang CK, Pan CC, Shew JY, Chang KJ, et al. Breast cancer cells induce cancer-associated fibroblasts to secrete hepatocyte growth factor to enhance breast tumorigenesis. PLoS ONE. 2011;6:e15313. doi: 10.1371/journal.pone.0015313 21249190

42. Calon A, Lonardo E, Berenguer-Llergo A, Espinet E, Hernando-Momblona X, Iglesias M, et al. Stromal gene expression defines poor-prognosis subtypes in colorectal cancer. Nat Genet. 2015;47:320–329. doi: 10.1038/ng.3225 25706628

43. Rivenbark AG, O’Connor SM, Coleman WB. Molecular and cellular heterogeneity in breast cancer: challenges for personalized medicine. Am J Pathol. 2013;183:1113–1124. doi: 10.1016/j.ajpath.2013.08.002 23993780

44. Engebraaten O, Vollan HK, Børresen-Dale AL. Triple-negative breast cancer and the need for new therapeutic targets. Am J Pathol. 2013;183:1064–1074. doi: 10.1016/j.ajpath.2013.05.033 23920327

45. De Abreu FB, Wells WA, Tsongalis GJ. The emerging role of the molecular diagnostics laboratory in breast cancer personalized medicine. Am J Pathol. 2013;183:1075–1083. doi: 10.1016/j.ajpath.2013.07.002 23920325

46. Blows FM, Driver KE, Schmidt MK, Broeks A, van Leeuwen FE, Wesseling J, et al. Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies. PLoS Med. 2010;7:e1000279. doi: 10.1371/journal.pmed.1000279 20520800

47. Ijichi H, Chytil A, Gorska AE, Aakre ME, Bierie B, Tada M, et al. Inhibiting Cxcr2 disrupts tumor-stromal interactions and improves survival in a mouse model of pancreatic ductal adenocarcinoma. J Clin Invest. 2011;121:4106–4117. doi: 10.1172/JCI42754 21926469

48. Giavazzi R, Garofalo A, Bani MR, Abbate M, Ghezzi P, Boraschi D, et al. Interleukin 1-induced augmentation of experimental metastases from a human melanoma in nude mice. Cancer Res. 1990;50:4771–4775. 2196116

49. Lewis AM, Varghese S, Xu H, Alexander HR. Interleukin-1 and cancer progression: the emerging role of interleukin-1 receptor antagonist as a novel therapeutic agent in cancer treatment. J Transl Med. 2006;4:48. 17096856

50. Dinarello CA. Why not treat human cancer with interleukin-1 blockade? Cancer Metastasis Rev. 2010;29:317–329. doi: 10.1007/s10555-010-9229-0 20422276

51. Tu S, Bhagat G, Cui G, Takaishi S, Kurt-Jones EA, Rickman B, et al Overexpression of interleukin-1beta induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice. Cancer Cell. 2008;14:408–419. doi: 10.1016/j.ccr.2008.10.011 18977329

52. Reed JR, Leon RP, Hall MK, Schwertfeger KL. Interleukin-1beta and fibroblast growth factor receptor 1 cooperate to induce cyclooxygenase-2 during early mammary tumourigenesis. Breast Cancer Res. 2009;11:R21. doi: 10.1186/bcr2246 19393083

53. Hong DS, Hui D, Bruera E, Janku F, Naing A, Falchook GS, et al. MABp1, a first-in-class true human antibody targeting interleukin-1α in refractory cancers: an open-label, phase 1 dose-escalation and expansion study. Lancet Oncol. 2014;15:656–666. doi: 10.1016/S1470-2045(14)70155-X 24746841

54. Kolb M, Margetts PJ, Sime PJ, Gauldie J. Proteoglycans decorin and biglycan differentially modulate TGF-beta-mediated fibrotic responses in the lung. Am J Physiol Lung Cell Mol Physiol. 2001;280:L1327–L1334. 11350814

55. Goldoni S, Iozzo RV. Tumor microenvironment: modulation by decorin and related molecules harboring leucine-rich tandem motifs. Int J Cancer. 2008;123:2473–2479. doi: 10.1002/ijc.23930 18798267

56. Neill T, Schaefer L, Iozzo RV. Decorin: a guardian from the matrix. Am J Pathol. 2012;181:380–387. doi: 10.1016/j.ajpath.2012.04.029 22735579

57. Wadhwa S, Embree MC, Bi Y, Young MF. Regulation, regulatory activities, and function of biglycan. Crit Rev Eukaryot Gene Expr. 2004;14:301–315. 15663360

58. Bianco P, Fisher LW, Young MF, Termine JD, Robey PG. Expression and localization of the two small proteoglycans biglycan and decorin in developing human skeletal and non-skeletal tissues. J Histochem Cytochem. 1990;38:1549–1563. 2212616

59. Bierie B, Moses HL. TGF-beta and cancer. Cytokine Growth Factor Rev. 2006;17:29–40. 16289860

60. Dumont N, Arteaga CL. Targeting the TGF beta signaling network in human neoplasia. Cancer Cell. 2003;3:531–536. 12842082

61. Siegel PM, Massagué J. Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer. Nat Rev Cancer. 2003;3:807–821. 14557817

62. Buck MB, Fritz P, Dippon J, Zugmaier G, Knabbe C. Prognostic significance of transforming growth factor beta receptor II in estrogen receptor-negative breast cancer patients. Clin Cancer Res. 2004;10:491–498. 14760070

63. Dalal BI, Keown PA, Greenberg AH. Immunocytochemical localization of secreted transforming growth factor-beta 1 to the advancing edges of primary tumors and to lymph node metastases of human mammary carcinoma. Am J Pathol. 1993;143:381–389. 8393616

64. Massagué J. TGFbeta in cancer. Cell. 2008;134:215–230. doi: 10.1016/j.cell.2008.07.001 18662538

65. Massagué J, Gomis RR. The logic of TGFbeta signaling. FEBS Lett. 2006;580:2811–2820. 16678165

66. Matise LA, Palmer TD, Ashby WJ, Nashabi A, Chytil A, Aakre M, et al. Lack of transforming growth factor-β signaling promotes collective cancer cell invasion through tumor-stromal crosstalk. Breast Cancer Res. 2012;14:R98. doi: 10.1186/bcr3217 22748014