Open Access

Upregulation of interleukin-8 and activin A induces osteoclastogenesis in ameloblastoma

  • Authors:
    • Xin Liu
    • Zhifeng Chen
    • Tianjun Lan
    • Peisheng Liang
    • Qian Tao
  • View Affiliations

  • Published online on: April 23, 2019     https://doi.org/10.3892/ijmm.2019.4171
  • Pages: 2329-2340
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ameloblastoma is a common odontogenic benign tumor located in the jaws and is characterized by severe local bone destruction. The current study aimed to investigate the effect of interactions between tumor cells and bone marrow stromal cells (BMSCs) on osteoclast formation in ameloblastoma. The impact of ameloblastoma/BMSC interactions on cytokine production, gene expression and osteoclastogenesis was examined using an immortalized ameloblastoma cell line that the authors' previously established. The results demonstrated that interactions between ameloblastoma cells and BMSCs increased interleukin (IL)‑8 and activin A secretion by BMSCs. IL‑8 expression in BMSCs was modulated by tumor‑derived tumor necrosis factor‑α and IL‑8 contributed to osteoclast formation not only directly but also by stimulating receptor activator of NF‑κB ligand (RANKL) expression in BMSCs. Activin A secretion in BMSCs was stimulated by ameloblastoma cells via cell‑to‑cell‑mediated activation of c‑Jun N‑terminal kinase activation, acting as a cofactor of RANKL to induce osteoclast formation and function. The present study highlights the critical role of communication between BMSCs and ameloblastoma cells in bone resorption in ameloblastoma.

References

1 

Jhamb T and Kramer JM: Molecular concepts in the pathogenesis of ameloblastoma: Implications for therapeutics. Exp Mol Pathol. 97:345–353. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Wright JM and Vered M: Update from the 4th edition of the world health organization classification of head and neck tumours: Odontogenic and maxillofacial bone tumors. Head Neck Pathol. 11:68–77. 2017. View Article : Google Scholar : PubMed/NCBI

3 

Sandra F, Hendarmin L, Kukita T, Nakao Y, Nakamura N and Nakamura S: Ameloblastoma induces osteoclastogenesis: A possible role of ameloblastoma in expanding in the bone. Oral Oncol. 41:637–644. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Ong'uti MN, Cruchley AT, Howells GL and Williams DM: Ki-67 antigen in ameloblastomas: Correlation with clinical and histological parameters in 54 cases from Kenya. Int J Oral Maxillofac Surg. 26:376–379. 1997. View Article : Google Scholar : PubMed/NCBI

5 

Sandra F, Mitsuyasu T, Nakamura N, Shiratsuchi Y and Ohishi M: Immunohistochemical evaluation of PCNA and Ki-67 in ameloblastoma. Oral Oncol. 37:193–198. 2001. View Article : Google Scholar : PubMed/NCBI

6 

Sandra F, Nakamura N, Mitsuyasu T, Shiratsuchi Y and Ohishi M: Two relatively distinct patterns of ameloblastoma: An anti-apoptotic proliferating site in the outer layer (periphery) and a pro-apoptotic differentiating site in the inner layer (centre). Histopathology. 39:93–98. 2001. View Article : Google Scholar : PubMed/NCBI

7 

Luo HY, Yu SF and Li TJ: Differential expression of apoptosis-related proteins in various cellular components of ameloblastomas. Int J Oral Maxillofac Surg. 35:750–755. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Jiang C, Zhang Q, Shanti RM, Shi S, Chang TH, Carrasco L, Alawi F and Le AD: Mesenchymal stromal cell-derived interleukin-6 promotes epithelial-mesenchymal transition and acquisition of epithelial stem-like cell properties in ameloblastoma epithelial cells. Stem Cells. 35:2083–2094. 2017. View Article : Google Scholar : PubMed/NCBI

9 

Zhang L, Zeng D, Huang H, Wang J, Tao Q, Pan C, Xu J, Zhang B and Wang A: Tissue inhibitor of metalloproteinase-2 inhibits ameloblastoma growth in a new mouse xenograft disease model. J Oral Pathol Med. 39:94–102. 2010. View Article : Google Scholar

10 

Zhang B, Zhang J, Huang HZ, Xu ZY and Xie HL: Expression and role of metalloproteinase-2 and endogenous tissue regulator in ameloblastoma. J Oral Pathol Med. 39:219–222. 2010. View Article : Google Scholar

11 

Wang A, Zhang B, Huang H, Zhang L, Zeng D, Tao Q, Wang J and Pan C: Suppression of local invasion of ameloblastoma by inhibition of matrix metalloproteinase-2 in vitro. BMC Cancer. 8:1822008. View Article : Google Scholar : PubMed/NCBI

12 

Martin TJ: Manipulating the environment of cancer cells in bone: A novel therapeutic approach. J Clin Invest. 110:1399–1401. 2002. View Article : Google Scholar : PubMed/NCBI

13 

Herrero AB, García-Gómez A, Garayoa M, Corchete LA, Hernández JM, San Miguel J and Gutierrez NC: Effects of IL-8 Up-regulation on cell survival and osteoclastogenesis in multiple myeloma. Am J Pathol. 186:2171–2182. 2016. View Article : Google Scholar : PubMed/NCBI

14 

Sottnik JL and Keller ET: Understanding and targeting osteoclastic activity in prostate cancer bone metastases. Curr Mol Med. 13:626–639. 2013. View Article : Google Scholar :

15 

Kovacic N, Croucher PI and McDonald MM: Signaling between tumor cells and the host bone marrow microenvironment. Calcif Tissue Int. 94:125–139. 2014. View Article : Google Scholar

16 

Mundy GR: Metastasis to bone: Causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2:584–593. 2002. View Article : Google Scholar : PubMed/NCBI

17 

Azim H and Azim HA Jr: Targeting RANKL in breast cancer: Bone metastasis and beyond. Expert Rev Anticancer Ther. 13:195–201. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Chen G, Sircar K, Aprikian A, Potti A, Goltzman D and Rabbani SA: Expression of RANKL/RANK/OPG in primary and metastatic human prostate cancer as markers of disease stage and functional regulation. Cancer. 107:289–298. 2006. View Article : Google Scholar : PubMed/NCBI

19 

Croucher PI, Shipman CM, Lippitt J, Perry M, Asosingh K, Hijzen A, Brabbs AC, van Beek EJ, Holen I, Skerry TM, et al: Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma. Blood. 98:3534–3540. 2001. View Article : Google Scholar : PubMed/NCBI

20 

Sezer O, Heider U, Jakob C, Eucker J and Possinger K: Human bone marrow myeloma cells express RANKL. J Clin Oncol. 20:353–354. 2002. View Article : Google Scholar : PubMed/NCBI

21 

Farrugia AN, Atkins GJ, To LB, Pan B, Horvath N, Kostakis P, Findlay DM, Bardy P and Zannettino AC: Receptor activator of nuclear factor-kappaB ligand expression by human myeloma cells mediates osteoclast formation in vitro and correlates with bone destruction in vivo. Cancer Res. 63:5438–5445. 2003.PubMed/NCBI

22 

Giuliani N, Bataille R, Mancini C, Lazzaretti M and Barillé S: Myeloma cells induce imbalance in the osteoprotegerin/osteoprotegerin ligand system in the human bone marrow environment. Blood. 98:3527–3533. 2001. View Article : Google Scholar : PubMed/NCBI

23 

Pearse RN, Sordillo EM, Yaccoby S, Wong BR, Liau DF, Colman N, Michaeli J, Epstein J and Choi Y: Multiple myeloma disrupts the TRANCE/osteoprotegerin cytokine axis to trigger bone destruction and promote tumor progression. Proc Natl Acad Sci USA. 98:11581–11586. 2001. View Article : Google Scholar

24 

Shipman CM and Croucher PI: Osteoprotegerin is a soluble decoy receptor for tumor necrosis factor-related apoptosis-inducing ligand/Apo2 ligand and can function as a paracrine survival factor for human myeloma cells. Cancer Res. 63:912–916. 2003.PubMed/NCBI

25 

Vallet S, Mukherjee S, Vaghela N, Hideshima T, Fulciniti M, Pozzi S, Santo L, Cirstea D, Patel K, Sohani AR, et al: Activin a promotes multiple myeloma-induced osteolysis and is a promising target for myeloma bone disease. Proc Natl Acad Sci USA. 107:5124–5129. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Renema N, Navet B, Heymann MF, Lezot F and Heymann D: RANK-RANKL signalling in cancer. Biosci Rep. 36:pii: e003662016. View Article : Google Scholar

27 

Chikatsu N, Takeuchi Y, Tamura Y, Fukumoto S, Yano K, Tsuda E, Ogata E and Fujita T: Interactions between cancer and bone marrow cells induce osteoclast differentiation factor expression and osteoclast-like cell formation in vitro. Biochem Biophys Res Commun. 267:632–637. 2000. View Article : Google Scholar : PubMed/NCBI

28 

Sisay M, Mengistu G and Edessa D: The RANK/RANKL/OPG system in tumorigenesis and metastasis of cancer stem cell: Potential targets for anticancer therapy. Onco Targets Ther. 10:3801–3810. 2017. View Article : Google Scholar : PubMed/NCBI

29 

Wada T, Nakashima T, Hiroshi N and Penninger JM: RANKL-RANK signaling in osteoclastogenesis and bone disease. Trends Mol Med. 12:17–25. 2006. View Article : Google Scholar

30 

Fuchigami T, Kibe T, Koyama H, Kishida S, Iijima M, Nishizawa Y, Hijioka H, Fujii T, Ueda M, Nakamura N, et al: Regulation of IL-6 and IL-8 production by reciprocal cell-to-cell interactions between tumor cells and stromal fibroblasts through IL-1α in ameloblastoma. Biochem Biophys Res Commun. 451:491–496. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Tao Q, Lv B, Qiao B, Zheng CQ and Chen ZF: Immortalization of ameloblastoma cells via reactivation of telomerase function: Phenotypic and molecular characteristics. Oral Oncol. 45:e239–e244. 2009. View Article : Google Scholar : PubMed/NCBI

32 

Wani MR, Fuller K, Kim NS, Choi Y and Chambers T: Prostaglandin E2 cooperates with TRANCE in osteoclast induction from hemopoietic precursors: Synergistic activation of differentiation, cell spreading, and fusion. Endocrinology. 140:1927–1935. 1999. View Article : Google Scholar : PubMed/NCBI

33 

Fuller K, Bayley KE and Chambers TJ: Activin A is an essential cofactor for osteoclast induction. Biochem Biophys Res Commun. 268:2–7. 2000. View Article : Google Scholar : PubMed/NCBI

34 

Ohta K, Naruse T, Ishida Y, Shigeishi H, Nakagawa T, Fukui A, Nishi H, Sasaki K, Ogawa I and Takechi M: TNF-α-induced IL-6 and MMP-9 expression in immortalized ameloblastoma cell line established by hTERT. Oral Dis. 23:199–209. 2017. View Article : Google Scholar

35 

Kline M, Donovan K, Wellik L, Lust C, Jin W, Moon-Tasson L, Xiong Y, Witzig TE, Kumar S, Rajkumar SV and Lust JA: Cytokine and chemokine profiles in multiple myeloma; signifi-cance of stromal interaction and correlation of IL-8 production with disease progression. Leuk Res. 31:591–598. 2007. View Article : Google Scholar

36 

Bendre MS, Margulies AG, Walser B, Akel NS, Bhattacharrya S, Skinner RA, Swain F, Ramani V, Mohammad KS, Wessner LL, et al: Tumor-derived interleukin-8 stimulates osteolysis independent of the receptor activator of nuclear factor-kappaB ligand pathway. Cancer Res. 65:11001–11009. 2005. View Article : Google Scholar : PubMed/NCBI

37 

Bendre MS, Montague DC, Peery T, Akel NS, Gaddy D and Suva LJ: Interleukin-8 stimulation of osteoclastogenesis and bone resorption is a mechanism for the increased osteolysis of metastatic bone disease. Bone. 33:28–37. 2003. View Article : Google Scholar : PubMed/NCBI

38 

Tanimoto K, Yoshida E, Mita S, Nibu Y, Murakami K and Fukamizu A: Human activin betaA gene. Identification of novel 5′ exon, functional promoter, and enhancers. J Biol Chem. 271:32760–32769. 1996. View Article : Google Scholar : PubMed/NCBI

39 

Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, et al: Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 93:165–176. 1998. View Article : Google Scholar : PubMed/NCBI

40 

Yoshimoto S, Morita H, Matsubara R, Mitsuyasu T, Imai Y, Kajioka S, Yoneda M, Ito Y, Hirofuji T, Nakamura S and Hirata M: Surface vacuolar ATPase in ameloblastoma contributes to tumor invasion of the jaw bone. Int J Oncol. 48:1258–1270. 2016. View Article : Google Scholar : PubMed/NCBI

41 

Suva LJ, Washam C, Nicholas RW and Griffin RJ: Bone metastasis: Mechanisms and therapeutic opportunities. Nat Rev Endocrinol. 7:208–218. 2011. View Article : Google Scholar : PubMed/NCBI

42 

Yoshimura T, Matsushima K, Tanaka S, Robinson EA, Appella E, Oppenheim JJ and Leonard EJ: Purification of a human monocyte-derived neutrophil chemotactic factor that has peptide sequence similarity to other host defense cytokines. Proc Natl Acad Sci USA. 84:9233–9237. 1987. View Article : Google Scholar : PubMed/NCBI

43 

Waugh DJ and Wilson C: The interleukin-8 pathway in cancer. Clin Cancer Res. 14:6735–6741. 2008. View Article : Google Scholar : PubMed/NCBI

44 

Kim SJ, Uehara H, Karashima T, McCarty M, Shih N and Fidler IJ: Expression of interleukin-8 correlates with angiogenesis, tumorigenicity, and metastasis of human prostate cancer cells implanted orthotopically in nude mice. Neoplasia. 3:33–42. 2001. View Article : Google Scholar : PubMed/NCBI

45 

Hwang YS, Lee SK, Park KK and Chung WY: Secretion of IL-6 and IL-8 from lysophosphatidic acid-stimulated oral squamous cell carcinoma promotes osteoclastogenesis and bone resorption. Oral Oncol. 48:40–48. 2012. View Article : Google Scholar

46 

Baud V and Karin M: Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biol. 11:372–377. 2001. View Article : Google Scholar : PubMed/NCBI

47 

da Silva TA, Batista AC, Mendonca EF, Leles CR, Fukada S and Cunha FQ: Comparative expression of RANK, RANKL, and OPG in keratocystic odontogenic tumors, ameloblastomas, and dentigerous cysts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 105:333–341. 2008. View Article : Google Scholar

48 

Siar CH, Tsujigiwa H, Ishak I, Hussin NM, Nagatsuka H and Ng KH: RANK, RANKL, and OPG in recurrent solid/multicystic amelo-blastoma: Their distribution patterns and biologic significance. Oral Surg Oral Med Oral Pathol Oral Radiol. 119:83–91. 2015. View Article : Google Scholar

49 

Vale W, Rivier J, Vaughan J, McClintock R, Corrigan A, Woo W, Karr D and Spiess J: Purification and characterization of an FSH releasing protein from porcine ovarian follicular fluid. Nature. 321:776–779. 1986. View Article : Google Scholar : PubMed/NCBI

50 

Xia Y and Schneyer AL: The biology of activin: Recent advances in structure, regulation and function. J Endocrinol. 202:1–12. 2009. View Article : Google Scholar : PubMed/NCBI

51 

Chen YG, Lui HM, Lin SL, Lee JM and Ying SY: Regulation of cell proliferation, apoptosis, and carcinogenesis by activin. Exp Biol Med (Maywood). 227:75–87. 2002. View Article : Google Scholar

52 

Chen YG, Wang Q, Lin SL, Chang CD, Chuang J and Ying SY: Activin signaling and its role in regulation of cell proliferation, apoptosis, and carcinogenesis. Exp Biol Med (Maywood). 231:534–544. 2006. View Article : Google Scholar

53 

Nicks KM, Perrien DS, Akel NS, Suva LJ and Gaddy D: Regulation of osteoblastogenesis and osteoclastogenesis by the other reproductive hormones, activin and inhibin. Mol Cell Endocrinol. 310:11–20. 2009. View Article : Google Scholar : PubMed/NCBI

54 

Kajita T, Ariyoshi W, Okinaga T, Mitsugi S, Tominaga K and Nishihara T: Mechanisms involved in enhancement of osteoclast formation by activin-A. J Cell Biochem. 119:6974–6985. 2018. View Article : Google Scholar : PubMed/NCBI

55 

Snider JL, Allison C, Bellaire BH, Ferrero RL and Cardelli JA: The beta1 integrin activates JNK independent of CagA, and JNK activation is required for Helicobacter pylori CagA+-induced motility of gastric cancer cells. J Biol Chem. 283:13952–13963. 2008. View Article : Google Scholar : PubMed/NCBI

56 

Ohshiba T, Miyaura C, Inada M and Ito A: Role of RANKL-induced osteoclast formation and MMP-dependent matrix degradation in bone destruction by breast cancer metastasis. Br J Cancer. 88:1318–1326. 2003. View Article : Google Scholar : PubMed/NCBI

57 

Zheng Y, Chow SO, Boernert K, Basel D, Mikuscheva A, Kim S, Fong-Yee C, Trivedi T, Buttgereit F, Sutherland RL, et al: Direct crosstalk between cancer and osteoblast lineage cells fuels metastatic growth in bone via auto-amplification of IL-6 and RANKL signaling pathways. J Bone Miner Res. 29:1938–1949. 2014. View Article : Google Scholar : PubMed/NCBI

58 

Bussard KM, Venzon DJ and Mastro AM: Osteoblasts are a major source of inflammatory cytokines in the tumor microenvironment of bone metastatic breast cancer. J Cell Biochem. 111:1138–1148. 2010. View Article : Google Scholar : PubMed/NCBI

59 

Sohara Y, Shimada H, Minkin C, Erdreich-Epstein A, Nolta JA and DeClerck YA: Bone marrow mesenchymal stem cells provide an alternate pathway of osteoclast activation and bone destruction by cancer cells. Cancer Res. 65:1129–1135. 2005. View Article : Google Scholar : PubMed/NCBI

60 

Qian Y and Huang HZ: The role of RANKL and MMP-9 in the bone resorption caused by ameloblastoma. J Oral Pathol Med. 39:592–598. 2010. View Article : Google Scholar : PubMed/NCBI

61 

Guénet JL: The mouse genome. Genome Res. 15:1729–1740. 2005. View Article : Google Scholar : PubMed/NCBI

62 

Cilvik SN, Wang JI, Lavine KJ, Uchida K, Castro A, Gierasch CM, Weinheimer CJ, House SL, Kovacs A, Nichols CG and Ornitz DM: Fibroblast growth factor receptor 1 signaling in adult cardiomyocytes increases contractility and results in a hypertrophic cardiomyopathy. PLoS One. 8:e829792013. View Article : Google Scholar : PubMed/NCBI

63 

Sunagar K, Fry BG, Jackson TN, Casewell NR, Undheim EA, Vidal N, Ali SA, King GF, Vasudevan K, Vasconcelos V and Antunes A: Molecular evolution of vertebrate neurotrophins: Co-option of the highly conserved nerve growth factor gene into the advanced snake venom arsenalf. PLoS One. 8:e818272013. View Article : Google Scholar : PubMed/NCBI

64 

Shen J, Li S and Chen D: TGF- β signaling and the development of osteoarthritis. Bone Res. 2:pii: 140022014. View Article : Google Scholar

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APA
Liu, X., Chen, Z., Lan, T., Liang, P., & Tao, Q. (2019). Upregulation of interleukin-8 and activin A induces osteoclastogenesis in ameloblastoma. International Journal of Molecular Medicine, 43, 2329-2340. https://doi.org/10.3892/ijmm.2019.4171
MLA
Liu, X., Chen, Z., Lan, T., Liang, P., Tao, Q."Upregulation of interleukin-8 and activin A induces osteoclastogenesis in ameloblastoma". International Journal of Molecular Medicine 43.6 (2019): 2329-2340.
Chicago
Liu, X., Chen, Z., Lan, T., Liang, P., Tao, Q."Upregulation of interleukin-8 and activin A induces osteoclastogenesis in ameloblastoma". International Journal of Molecular Medicine 43, no. 6 (2019): 2329-2340. https://doi.org/10.3892/ijmm.2019.4171