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01-12-2020 | Research

Role of hypoxia-related proteins in adenoid cystic carcinoma invasion

Authors: Raíssa Pinheiro de Mendonça, Giordanna Pereira Chemelo, Geovanni Pereira Mitre, Dimitra Castelo Branco, Natacha Malu Miranda da Costa, Fabrício Mesquita Tuji, Maria Sueli da Silva Kataoka, Ricardo Alves Mesquita, Sérgio de Melo Alves Júnior, João de Jesus Viana Pinheiro

Published in: Diagnostic Pathology | Issue 1/2020

Abstract

Background

Among cancers affecting the oral cavity, adenoid cystic carcinoma (ACC) is a relatively common malignant neoplasm. It has high rates of metastasis and recurrence and is associated with significant morbidity. During the progression of ACC, the oxygen concentration is reduced in specific areas of the tumour microenvironment, leading to intratumoural hypoxia. The expression of NOTCH1, a disintegrin and metalloproteinase 12 (ADAM-12), hypoxia-inducible factor 1 alpha (HIF-1α), and heparin-binding epidermal growth factor (HB-EGF) under hypoxic conditions has been implicated in invadopodia formation, tumour invasiveness, and metastasis. The aim of this study was to analyse the expression of these proteins to elucidate the mechanisms underlying ACC invasiveness.

Methods

Fifteen ACC samples and 10 normal-looking salivary gland (SG) samples were used to investigate the expression of these proteins by immunohistochemistry. Primary antibodies against NOTCH1, ADAM-12, HIF-1α, and HB-EGF were used.

Results

The immunoexpression of all proteins was higher in ACC samples than in SG samples (p < 0.05).

Conclusions

There was increased expression of proteins associated with hypoxia and tumour invasiveness in ACC samples, which indicates a possible role of these proteins in the biological behaviour of this tumour.

Khafif A, Anavi Y, Haviv J, Fienmesser R, Calderon S, Marshak G. Adenoid cystic carcinoma of the salivary glands: a 20-year review with long-term follow-up. Ear Nose Throat J. 2005;84(10):662 664–667.CrossRef

Khan AJ, Digiovanna MP, Ross DA, et al. Adenoid cystic carcinoma: a retrospective clinical review. Int J Cancer. 2001;96(3):149–58. https://doi.org/10.1002/ijc.1013.CrossRefPubMed

Neville B, Damm DD, Allen C, Bouquot J. Oral and maxillofacial pathology, vol. 476. 3rd ed. St. Louis, Missouri: Elsevier; 2009. p. 497.

Buccione R, Caldieri G, Avala I. Invadopodia: specialized tumor cells structures for the focal degradation of the extracellular matrix. Cancer Metastasis Rev. 2009;28(1–2):137–49. https://doi.org/10.1007/s10555-008-9176-1.CrossRefPubMed

Linder S. The matrix corroded: podosomes and invadopodia in extracellular matrix degradation. Trends Cell Biol. 2007;17(3):107–17. https://doi.org/10.1016/j.tcb.2007.01.002.CrossRefPubMed

Nascimento CF, Gama-De-Souza LN, Freitas VM, Jaeger RG. Role of MMP9 on invadopodia formation in cells from adenoid cystic carcinoma. Study by laser scanning confocal microscopy. Microsc Res Tech. 2010;73(2):99–108. https://doi.org/10.1002/jemt.20761.CrossRefPubMed

Díaz B, Yuen A, Iizuka S, Higashiyama S, Courtneidge SA. Notch increases the shedding of HB-EGF by ADAM12 to potentiate invadopodia formation in hypoxia. J Cell Biol. 2013;201(2):279–92. https://doi.org/10.1083/jcb.201209151.CrossRefPubMedPubMedCentral

Gould CM, Courtneidge SA. Regulation of invadopodia by the tumor microenvironment. Cell Adhes Migr. 2014;8(3):226–35. https://doi.org/10.4161/cam.28346.CrossRef

Hashim NF, Nicholas NS, Dart AE, Kiriakidis S, Paleolog E, Wells CM. Hypoxia-induced invadopodia formation: a role for b-PIX. Open Biol. 2013;3(6):120159. https://doi.org/10.1098/rsob.120159.CrossRef

10.

Adelman DM, Gertsenstein M, Nagy A, Simon MC, Maltepe E. Placental cell fates are regulated in vivo by HIF-mediated hypoxia responses. Genes Dev. 2000;14(24):3191–203. https://doi.org/10.1101/gad.853700.CrossRefPubMedPubMedCentral

11.

Marcu LG, Harriss-Phillips WM, Filip SM. Hypoxia in head and neck cancer in theory and practice: a PET-based imaging approach. Comput Math Methods Med. 2014;2014:624–42. https://doi.org/10.1155/2014/624642.CrossRef

12.

Lee SS, Tsai CH, Yang SF, Ho YC, Chang YC. Hypoxia inducible factor-1a expression in areca quid chewing-associated oral squamous cell carcinomas. Oral Dis. 2010;16(7):696–701. https://doi.org/10.1111/j.1601-0825.2010.01680.x.CrossRefPubMed

13.

Cowden Dahl KD, Robertson SE, Weaver VM, Simon MC. Hypoxia-inducible factor regulates alphavbeta3 integrin cell surface expression. Mol Biol Cell. 2005;16(4):1901–12. https://doi.org/10.1091/mbc.e04-12-1082.CrossRefPubMedPubMedCentral

14.

Talks KL, Turley H, Gatter KC, et al. The expression and distribution of the hypoxia-inducible factors HIF-1alpha and HIF-2alpha in normal human tissues, cancers, and tumor-associated macrophages. Am J Pathol. 2000;157(2):411–21. https://doi.org/10.1016/s0002-9440(10)64554-3.CrossRefPubMedPubMedCentral

15.

Qi Y, Duhachek-Muggy S, Li H, Zolkiewska A. Phenotypic diversity of breast cancer-related mutations in metalloproteinase-disintegrin ADAM12. PLoS One. 2014;9(3):e92536. https://doi.org/10.1371/journal.pone.0092536.CrossRefPubMedPubMedCentral

16.

Najy AJ, Day KC, Day ML. ADAM15 supports prostate cancer metastasis by modulating tumor cell-endothelial cell interaction. Cancer Res. 2008;68(4):1092–9. https://doi.org/10.1158/0008-5472.CAN-07-2432.CrossRefPubMed

17.

Duffy MJ, McKiernan E, O'Donovan N, McGowan PM. Role of ADAMs in cancer formation and progression. Clin Cancer Res. 2009;15(4):1140–4. https://doi.org/10.1158/1078-0432.CCR-08-1585.CrossRefPubMed

18.

Mochizuki S, Okada Y. ADAMs in cancer cell proliferation and progression. Cancer Sci. 2007;98(5):621–8. https://doi.org/10.1111/j.1349-7006.2007.00434.x.CrossRefPubMed

19.

Baselga J, Arteaga CL. Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. J Clin Oncol. 2005;23(11):2445–59. https://doi.org/10.1200/JCO.2005.11.890.CrossRefPubMed

20.

Asakura M, Kitakaze M, Takashima S, et al. Cardiac hypertrophy is inhibited by antagonism of ADAM12 processing of HB-EGF: metalloproteinase inhibitors as a new therapy. Nat Med. 2002;8(1):35–40. https://doi.org/10.1038/nm0102-35.CrossRefPubMed

21.

Takebe N, Nguyen D, Yang SX. Targeting notch signaling pathway in cancer: clinical development advances and challenges. Pharmacol Ther. 2014;141(2):140–9. https://doi.org/10.1016/j.pharmthera.2013.09.005.CrossRefPubMed

22.

Li H, Solomon E, Duhachek Muggy S, Sun D, Zolkiewska A. Metalloprotease-disintegrin ADAM12 expression is regulated by notch signaling via microRNA-29. J Biol Chem. 2011;286(24):21500–10. https://doi.org/10.1074/jbc.M110.207951.CrossRefPubMedPubMedCentral

23.

Zhu H, Zhou X, Redfield S, He Z, Lewin J, Miele L. Elevated expression of notch1 is associated with metastasis of human malignancies. Int J Surg Pathol. 2013;21(5):449–54. https://doi.org/10.1177/1066896913496146.CrossRefPubMed

24.

Gustafsson MV, Zheng X, Pereira T, et al. Hypoxia requires notch signaling to maintain the undifferentiated cell state. Dev Cell. 2005;9(5):617–28. https://doi.org/10.1016/j.devcel.2005.09.010.CrossRefPubMed

25.

Weber KB, Shroyer KR, Heinz DE, Nawaz S, Said MS, Haugen BR. The use of a combination of galectin-3 and thyroid peroxidase for the diagnosis and prognosis of thyroid cancer. Am J Clin Pathol. 2004;122:524–31. https://doi.org/10.1309/UUQT-E505-PTN5-QJ7M.CrossRefPubMed

26.

Coca-Pelaz A, Rodrigo JP, Bradley PJ, Poorten VV, Triantafyllou A, Hunt JL, Strojan P, Rinaldo A, Haigentz M Jr, Takes RP, Mondin V, Teymoortash A, Thompsonm LDR, Ferlito A. Adenoid cystic carcinoma of the head and neck – An update. Oral Oncology. 2015;51:652–61. https://doi.org/10.1016/j.oraloncology.2015.04.005.CrossRefPubMed

27.

Stoeltzing O, McCarty MF, Wey JS, et al. Role of hypoxia-inducible factor 1alpha in gastric cancer cell growth, angiogenesis, and vessel maturation. J Natl Cancer Inst. 2004;96:946–56. https://doi.org/10.1093/jnci/djh168.CrossRefPubMed

28.

Samanta D, Gilkes DM, Chaturvedi P, Xiang L, Semenza GL. Hypoxia-inducible factors are required for chemotherapy resistance of breast cancer stem cells. Proc Natl Acad Sci U S A. 2014;111:E5429–38. https://doi.org/10.1073/pnas.1421438111.CrossRefPubMedPubMedCentral

29.

Harada H. How can we overcome tumor hypoxia in radiation therapy? J Radiat Res. 2011;52:545–56. https://doi.org/10.1269/jrr.11056.CrossRefPubMed

30.

Costa AF, Tasso MG, Mariano FV, et al. Levels and patterns of expression of hypoxia-inducible factor-1a, vascular endothelial growth factor, glucose transporter-1 and CD105 in adenoid cystic carcinomas with high-grade transformation. Histopathology. 2012;60(5):816–25. https://doi.org/10.1111/j.1365-2559.2011.04128.x.CrossRefPubMed

31.

Xiao C, Pan Y, Zeng X, Wang L, Li Z, Yan S, Wang H. Downregulation of hypoxia-inducible factor-1α inhibits growth, invasion, and angiogenesis of human salivary adenoid cystic carcinoma cells under hypoxia. Oncol Rep. 2018;40(3):1675–83. https://doi.org/10.3892/or.2018.6559.CrossRefPubMed

32.

Greer SN, Metcalf JL, Wang Y, Ohh M. The updated biology of hypoxia-inducible factor. EMBO J. 2012;31(11):2448–60. https://doi.org/10.1038/emboj.2012.125.CrossRefPubMedPubMedCentral

33.

Hockel M, Vaupel P. Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst. 2001;93:266–76. https://doi.org/10.1093/jnci/93.4.266.CrossRefPubMed

34.

Nyren-Erickson EK, Jones JM, Srivastava DK, et al. A disintegrin and metalloproteinase-12 (ADAM12): function, roles in disease progression, and clinical implications. Biochim Biophys Acta. 2013;1830(10):4445–55. https://doi.org/10.1016/j.bbagen.2013.05.011.CrossRefPubMedPubMedCentral

35.

Pinheiro JJV, Freitas VM, Moretti AIS, Jorge AG, Jaeger RG. Local invasiveness of ameloblastoma. Role played by matrix metalloproteinases and proliferative activity. Histopathology. 2004 Jul;45(1):65–72. https://doi.org/10.1111/j.1365-2559.2004.01902.x.CrossRefPubMed

36.

da Costa NM, Fialho AD, Proietti CC, et al. Role of hypoxia-related proteins in invasion of ameloblastoma cells: crosstalk between NOTCH1, hypoxia-inducible factor 1a, a disintegrin and metalloproteinase 12, and heparin-binding epidermal growth factor. Histopathology. 2016;69(1):99–106. https://doi.org/10.1111/his.12922.CrossRefPubMed

37.

Branco DC, Costa NMM, Abe CTS, Kataoka MSS, Pinheiro JJV, Alves-Junior SM. HIF-1, NOTCH1, ADAM12 and HB-EGF are overexpressed in mucoepidermoid carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol. 2019;127(1):e8–e17. https://doi.org/10.1016/j.oooo.2018.09.013.CrossRefPubMed

38.

Silva SV, Lima MA, Cella N, Jaeger RG, Freitas VM. ADAMTS-1 is found in the nuclei of normal and tumoral breast cells. PLoS One. 2016;11(10):e0165061. https://doi.org/10.1371/journal.pone.0165061.CrossRefPubMedPubMedCentral

39.

Mannello F, Medda V. Nuclear localization of matrix metalloproteinases. Prog Histochem Cytochem. 2012;47:27–58. https://doi.org/10.1016/j.proghi.2011.12.002.CrossRefPubMed

40.

Si-Tayeb K, Monvoisin A, Mazzocco C, et al. Matrix metalloproteinase 3 is present in the cell nucleus and is involved in apoptosis. Am J Pathol. 2006;169:1390–401. https://doi.org/10.2353/ajpath.2006.060005.CrossRefPubMedPubMedCentral

41.

Shao S, Li Z, Gao W, Yu G, Liu D, Pan F. ADAM-12 as a diagnostic marker for the proliferation, migration and invasion in patients with small cell lung cancer. PLoS One. 2014;9(1):e85936. https://doi.org/10.1371/journal.pone.0085936.CrossRefPubMedPubMedCentral

42.

Hieda M, Isokane M, Koizumi M, et al. Membrane-anchored growth factor, HB-EGF, on the cell surface targeted to the inner nuclear membrane. J Cell Biol Feb. 2008;180(4):763–9. https://doi.org/10.1083/jcb.200710022.CrossRef

43.

Nanba D, Mammoto A, Hashimoto K, et al. Proteolytic release of the carboxy-terminal fragment of proHB-EGF causes nuclear export of PLZF. J Cell Biol. 2003;163(3):489–502. https://doi.org/10.1083/jcb.200303017.CrossRefPubMedPubMedCentral

44.

Kinugasa Y, Hieda M, Hori M, et al. The carboxyl-terminal fragment of pro-HB-EGF reverses Bcl6-mediated gene repression. J Biol Chem. 2007;282(20):14797–806. https://doi.org/10.1074/jbc.M611036200.CrossRefPubMed

45.

Adam RM. Role of HB-EGF in cancer. Atlas Genet Cytogenet Oncol Haematol. 2011;15(7):610–9.

46.

Zheng LQ, Li SY, Li CX. Expression profiling analysis of autophagy-related genes in perineural invasion of cutaneous squamous cell carcinoma. Oncol Lett. 2018;15(4):4837–48. https://doi.org/10.3892/ol.2018.7971.CrossRefPubMedPubMedCentral

47.

Song Z, Ren H, Gao S, Zhao X, Zhang H, Hao J. The clinical significance and regulation mechanism of hypoxia-inducible factor-1 and miR-191 expression in pancreatic cancer. Tumour Biol. 2014;11:11319–28. https://doi.org/10.1007/s13277-014-2452-5.CrossRef

Title: Role of hypoxia-related proteins in adenoid cystic carcinoma invasion
Authors: Raíssa Pinheiro de Mendonça
Giordanna Pereira Chemelo
Geovanni Pereira Mitre
Dimitra Castelo Branco
Natacha Malu Miranda da Costa
Fabrício Mesquita Tuji
Maria Sueli da Silva Kataoka
Ricardo Alves Mesquita
Sérgio de Melo Alves Júnior
João de Jesus Viana Pinheiro
Publication date: 01-12-2020
Publisher: BioMed Central
Published in: Diagnostic Pathology / Issue 1/2020
Electronic ISSN: 1746-1596
DOI: https://doi.org/10.1186/s13000-020-00967-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Role of hypoxia-related proteins in adenoid cystic carcinoma invasion

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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