Adipophilin Immunoexpression And Its Pathophysiology In Human Tooth Germ And Ameloblastoma
Main Article Content
Keywords
Ameloblastoma, tooth germ, adipophilin, odontogenic tumor, immunoexpression
Abstract
Background: The process of tooth development is the result of a series of interactions between the ectoderm of the oral cavity and the neural crest ectomesenchyme. Ameloblastoma is a slow-growing, locally invasive odontogenic epithelial tumor that primarily develops from enamel tissue that has not undergone differentiation. The role of lipids in the histogenesis of tooth germ and pathogenesis of ameloblastoma is an area that has not been explored. Recently, interest has been drawn to the field of study of abnormal lipid metabolism in tumors. Adipophilin is a perilipin interacting protein that coats the exteriors of cytoplasmic lipid droplets. Elevated lipogenesis has been linked to poor prognosis in various tumors, suggesting potential therapeutic targets.
Aim: immunohistochemical expression of adipophilin in human tooth germ and ameloblastoma. Materials and methods: Fifteen samples each of formalin-fixed, paraffin-embedded ameloblastoma and human tissue tooth germ were taken. Immunohistochemical expression of adipophilin was done and scored. Comparative analyses were performed using the Kruskal-Wallis test along with Spearman's correlation.
Results: Adipophilin was positive in all the tooth germ samples and the staining intensity was predominantly moderate (73.3%), with consistent staining shown in the epithelial components in all stages. Adipophilin was positive in 12 out of 15 ameloblastomas with strong immunostaining (80%). Consistent staining was present in peripheral cells and few central cells.
Conclusion: The diffuse cytoplasmic positivity of adipophilin in ameloblastoma indicates the production and accumulation of lipid droplets, offering new evidence of metabolic alterations that may be involved in tumor progression. For a better understanding of the idea, molecular analysis of the signaling pathways linked to the mechanism of adipophilin in ameloblastoma is required.
References
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31. Ho J-N, Kim O-K, Nam D-E, Jun W, Lee J. Pycnogenol supplementation promotes lipolysis via activation of cAMP-dependent PKA in ob/ob mice and primary-cultured adipocytes. J Nutr Sci Vitaminol . 2014;60: 429–435.
32. Lee Y-M, Shin S-Y, Jue S-S, Kwon I-K, Cho E-H, Cho E-S, et al. The role of PIN1 on odontogenic and adipogenic differentiation in human dental pulp stem cells. Stem Cells Dev. 2014;23: 618–630.
33. Itabe H, Yamaguchi T, Nimura S, Sasabe N. Perilipins: a diversity of intracellular lipid droplet proteins. Lipids Health Dis. 2017;16: 83.
34. Paramasivam A. Plasma circulating tumor DNA as a molecular marker for oral cancer. Oral Oncol. 2022;130: 105926.
35. Vasanthi V, Ramadoss R. Secretory carcinoma of salivary gland - A systematic review of pediatric case reports and case series. J Oral Maxillofac Pathol. 2021;25: 327–331.
36. Lakshmi TA, Narasimhan M, Harikrishnan T, Rajan ST. Centromere Protein F (CENPF): A novel marker for salivary gland pathology. J Oral Maxillofac Pathol. 2022;26: 370–375.
37. Baez RV. Non-Alcoholic Fatty Liver Disease: Molecular Bases, Prevention and Treatment. BoD – Books on Demand; 2018.
38. Prasad M, Veeraraghavan VP, Jayaraman S. Tumorigenic potential of GLUT4: A therapeutic target for head and neck squamous cell carcinoma. Oral Oncol. 2022;133: 106061.
39. Selvaraj J, Yasothkumar D, Vishnu Priya V, Raj AT, Babu SD, Patil S. Development and tumorigenic potential of TP53: A therapeutic target for head and neck squamous cell carcinoma. Oral Oncol. 2022;130: 105922.
40. Dos Santos HT, Silva RN, Piña AR, de Souza do Nascimento J, de Almeida OP, Egal ESA, et al. Lipid droplets are involved in the process of high-grade transformation of adenoid cystic carcinoma. Histopathology. 2016;69: 160–162.
41. Balachander K, Paramasivam A. Selective autophagy as a potential therapeutic target for oral cancer. Oral Oncol. 2022;130: 105934.
42. Anand R, Pandiar D, Ramani P, Kamboj M. Field cancerization revisited in purview of
quantum entanglement: Delving into the unexplored. Oral Oncol. 2022;125: 105704.
43. Soares CD, Morais TML, Carlos R, Jorge J, de Almeida OP, de Carvalho MGF, et al. Sebaceous adenocarcinomas of the major salivary glands: a clinicopathological analysis of 10 cases. Histopathology. 2018;73: 585–592.
44. Hoang MP. Immunohistochemistry in Diagnostic Dermatopathology. Cambridge University Press; 2017.
45. Du W, Zhang L, Brett-Morris A, Aguila B, Kerner J, Hoppel CL, et al. HIF drives lipid deposition and cancer in ccRCC via repression of fatty acid metabolism. Nat Commun. 2017;8: 1769.
46. Shree Harini K, Ezhilarasan D, Elumalai P. Restoring the anti-tumor property of PTEN: A promising oral cancer treatment. Oral Oncol. 2022;134: 106113.
47. Yu X, Mi S, Ye J, Lou G. Aberrant lipid metabolism in cancer cells and tumor microenvironment: the player rather than bystander in cancer progression and metastasis. J Cancer. 2021;12: 7498–7506.
48. Li Y. Lipid Metabolism in Tumor Immunity. Springer Nature; 2021.
49. Jayaraman S, Pazhani J, PriyaVeeraraghavan V, Raj AT, Somasundaram DB, Patil S. PCNA and Ki67: Prognostic proliferation markers for oral cancer. Oral Oncol. 2022;130: 105943.
50. Li Z, Zhang H. Reprogramming of glucose, fatty acid and amino acid metabolism for cancer progression. Cell Mol Life Sci. 2016;73: 377–392.
51. Zhao Q, Lin X, Wang G. Targeting SREBP-1-Mediated Lipogenesis as Potential Strategies for Cancer. Front Oncol. 2022;12: 952371.
52. Johnson AM, Kleczko EK, Nemenoff RA. Eicosanoids in Cancer: New Roles in Immunoregulation. Front Pharmacol. 2020;11: 595498.
53. Bozza PT, Bakker-Abreu I, Navarro-Xavier RA, Bandeira-Melo C. Lipid body function in eicosanoid synthesis: an update. Prostaglandins Leukot Essent Fatty Acids. 2011;85: 205–213.
54. Cruz ALS, Carrossini N, Teixeira LK, Ribeiro-Pinto LF, Bozza PT, Viola JPB. Cell Cycle Progression Regulates Biogenesis and Cellular Localization of Lipid Droplets. Mol Cell Biol. 2019;39. doi:10.1128/MCB.00374-18
55. Tan R, Wang W, Wang S, Wang Z, Sun L, He W, et al. Small GTPase Rab40c associates with lipid droplets and modulates the biogenesis of lipid droplets. PLoS One. 2013;8: e63213.
2. Yu T, Klein OD. Molecular and cellular mechanisms of tooth development, homeostasis and repair. Development. 2020;147. doi:10.1242/dev.184754
3. Ahtiainen L, Uski I, Thesleff I, Mikkola ML. Early epithelial signaling center governs tooth budding morphogenesis. J Cell Biol. 2016;214: 753–767.
4. Fu Y, Miyazaki K, Chiba Y, Funada K, Yuta T, Tian T, et al. Identification of GPI-anchored protein LYPD1 as an essential factor for odontoblast differentiation in tooth development. J Biol Chem. 2023; 104638.
5. Masthan KMK, Anitha N, Krupaa J, Manikkam S. Ameloblastoma. J Pharm Bioallied Sci. 2015;7: S167–70.
6. Pradeep, Associate Professor, Department of Oral And Maxillofacial Surgery, Saveetha Dental college & Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University. Unicystic ameloblastoma: Case reports and review of literature Pradeep D. Int J Dent Oral Sci. 2021; 3412–3415.
7. Black D. Preliminary report on the sinanthropus lower jaw specimens recovered from the Chou Kou Tien cave deposit in 1930 and 1931. Bull Geol Soc China. 2009;11: 241–246.
8. Miginiac E. Influence des racines sur le developpement vegetatif ou floral des bourgeons cotyledonaires chez le Scrofularia arguta: role possible des cytokinines. Physiol Plant. 1971;25: 234–239.
9. Arumugam P, George R, Jayaseelan VP. Aberrations of m6A regulators are associated with tumorigenesis and metastasis in head and neck squamous cell carcinoma. Arch Oral Biol. 2021;122: 105030.
10. Gale N, Poljak M, Zidar N. Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: What is New in the 2017 WHO Blue Book for Tumours of the Hypopharynx, Larynx, Trachea and Parapharyngeal Space. Head Neck Pathol. 2017;11: 23–32.
11. Pandiar D, Ramani P, Shameena PM, Krishnan RP, Monica K. Adenoid ameloblastoma: A neglected variant of ameloblastoma or a separate entity? Oral Oncol. 2022;125: 105681.
12. Hendra FN, Van Cann EM, Helder MN, Ruslin M, de Visscher JG, Forouzanfar T, et al. Global incidence and profile of ameloblastoma: A systematic review and meta-analysis. Oral Dis. 2020;26: 12–21.
13. Osterne RLV, Brito RG de M, Alves APNN, Cavalcante RB, Sousa FB. Odontogenic tumors: a 5-year retrospective study in a Brazilian population and analysis of 3406 cases reported in the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;111: 474–481.
14. Pradeep, Senior Lecturer, Department of Conservative Dentistry and Endodontics, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University. Unicystic Mural Ameloblastoma: An Case Report and Review of litrature. Int J Dent Oral Sci. 2021; 3534–3537.
15. Ramani P, Krishnan RP, Pandiar D, Thamilselvan S. A rare combined motley variety of odontogenic tumors - Hybrid lesion or a new entity? Oral Oncol. 2022;124: 105521.
16. Chae MP, Smoll NR, Hunter-Smith DJ, Rozen WM. Establishing the natural history and growth rate of ameloblastoma with implications for management: systematic review and meta-analysis. PLoS One. 2015;10: e0117241.
17. Ramani P, Krishnan RP, Pandiar D, Behera A, Ramasubramanian A. Squamous odontogenic tumor like proliferations in dentigerous cyst- a great mimicker. Oral Oncol. 2022;125: 105699.
18. Khan W, Augustine D, Rao RS, Patil S, Awan KH, Sowmya SV, et al. Lipid metabolism in cancer: A systematic review. J Carcinog. 2021;20: 4.
19. Olzmann JA, Carvalho P. Dynamics and functions of lipid droplets. Nat Rev Mol Cell Biol. 2019;20: 137–155.
20. Straub BK, Gyoengyoesi B, Koenig M, Hashani M, Pawella LM, Herpel E, et al. Adipophilin/perilipin-2 as a lipid droplet-specific marker for metabolically active cells and diseases associated with metabolic dysregulation. Histopathology. 2013;62: 617–631.
21. Shinzawa-Itoh K, Aoyama H, Muramoto K, Terada H, Kurauchi T, Tadehara Y, et al. Structures and physiological roles of 13 integral lipids of bovine heart cytochrome c oxidase. EMBO J. 2007;26: 1713–1725.
22. Torres M, Parets S, Fernández-Díaz J, Beteta-Göbel R, Rodríguez-Lorca R, Román R, et al. Lipids in Pathophysiology and Development of the Membrane Lipid Therapy: New Bioactive Lipids. Membranes . 2021;11. doi:10.3390/membranes11120919
23. Orlicky DJ, Degala G, Greenwood C, Bales ES, Russell TD, McManaman JL. Multiple functions encoded by the N-terminal PAT domain of adipophilin. J Cell Sci. 2008;121: 2921–2929.
24. Meadows JW, Pitzer B, Brockman DE, Myatt L. Expression and localization of adipophilin and perilipin in human fetal membranes: association with lipid bodies and enzymes involved in prostaglandin synthesis. J Clin Endocrinol Metab. 2005;90: 2344–2350.
25. Kurotaki Y, Sakai N, Miyazaki T, Hosonuma M, Sato Y, Karakawa A, et al. Effects of lipid metabolism on mouse incisor dentinogenesis. Sci Rep. 2020;10: 5102.
26. French LE, Hahne M, Viard I, Radlgruber G, Zanone R, Becker K, et al. Fas and Fas ligand in embryos and adult mice: ligand expression in several immune-privileged tissues and coexpression in adult tissues characterized by apoptotic cell turnover. J Cell Biol. 1996;133: 335–343.
27. Nat R, Radu E, Regalia T, Popescu LM. Apoptosis in human embryo development: 3. Fas-induced apoptosis in brain primary cultures. J Cell Mol Med. 2001;5: 417–428.
28. Yi H, Xue L, Guo M-X, Ma J, Zeng Y, Wang W, et al. Gene expression atlas for human embryogenesis. FASEB J. 2010;24: 3341–3350.
29. Matalova E, Tucker AS, Misek I. Apoptosis-related factors (Fas receptor, Fas ligand, FADD) in early tooth development of the field vole (Microtus agrestis). Arch Oral Biol. 2005;50: 165–169.
30. Sánchez-Romero C, Carreón-Burciaga R, Gónzalez-Gónzalez R, Villarroel-Dorrego M, Molina-Frechero N, Bologna-Molina R. Perilipin 1 and adipophilin immunoexpression suggests the presence of lipid droplets in tooth germ, ameloblastoma, and ameloblastic carcinoma. J Oral Pathol Med. 2021;50: 708–715.
31. Ho J-N, Kim O-K, Nam D-E, Jun W, Lee J. Pycnogenol supplementation promotes lipolysis via activation of cAMP-dependent PKA in ob/ob mice and primary-cultured adipocytes. J Nutr Sci Vitaminol . 2014;60: 429–435.
32. Lee Y-M, Shin S-Y, Jue S-S, Kwon I-K, Cho E-H, Cho E-S, et al. The role of PIN1 on odontogenic and adipogenic differentiation in human dental pulp stem cells. Stem Cells Dev. 2014;23: 618–630.
33. Itabe H, Yamaguchi T, Nimura S, Sasabe N. Perilipins: a diversity of intracellular lipid droplet proteins. Lipids Health Dis. 2017;16: 83.
34. Paramasivam A. Plasma circulating tumor DNA as a molecular marker for oral cancer. Oral Oncol. 2022;130: 105926.
35. Vasanthi V, Ramadoss R. Secretory carcinoma of salivary gland - A systematic review of pediatric case reports and case series. J Oral Maxillofac Pathol. 2021;25: 327–331.
36. Lakshmi TA, Narasimhan M, Harikrishnan T, Rajan ST. Centromere Protein F (CENPF): A novel marker for salivary gland pathology. J Oral Maxillofac Pathol. 2022;26: 370–375.
37. Baez RV. Non-Alcoholic Fatty Liver Disease: Molecular Bases, Prevention and Treatment. BoD – Books on Demand; 2018.
38. Prasad M, Veeraraghavan VP, Jayaraman S. Tumorigenic potential of GLUT4: A therapeutic target for head and neck squamous cell carcinoma. Oral Oncol. 2022;133: 106061.
39. Selvaraj J, Yasothkumar D, Vishnu Priya V, Raj AT, Babu SD, Patil S. Development and tumorigenic potential of TP53: A therapeutic target for head and neck squamous cell carcinoma. Oral Oncol. 2022;130: 105922.
40. Dos Santos HT, Silva RN, Piña AR, de Souza do Nascimento J, de Almeida OP, Egal ESA, et al. Lipid droplets are involved in the process of high-grade transformation of adenoid cystic carcinoma. Histopathology. 2016;69: 160–162.
41. Balachander K, Paramasivam A. Selective autophagy as a potential therapeutic target for oral cancer. Oral Oncol. 2022;130: 105934.
42. Anand R, Pandiar D, Ramani P, Kamboj M. Field cancerization revisited in purview of
quantum entanglement: Delving into the unexplored. Oral Oncol. 2022;125: 105704.
43. Soares CD, Morais TML, Carlos R, Jorge J, de Almeida OP, de Carvalho MGF, et al. Sebaceous adenocarcinomas of the major salivary glands: a clinicopathological analysis of 10 cases. Histopathology. 2018;73: 585–592.
44. Hoang MP. Immunohistochemistry in Diagnostic Dermatopathology. Cambridge University Press; 2017.
45. Du W, Zhang L, Brett-Morris A, Aguila B, Kerner J, Hoppel CL, et al. HIF drives lipid deposition and cancer in ccRCC via repression of fatty acid metabolism. Nat Commun. 2017;8: 1769.
46. Shree Harini K, Ezhilarasan D, Elumalai P. Restoring the anti-tumor property of PTEN: A promising oral cancer treatment. Oral Oncol. 2022;134: 106113.
47. Yu X, Mi S, Ye J, Lou G. Aberrant lipid metabolism in cancer cells and tumor microenvironment: the player rather than bystander in cancer progression and metastasis. J Cancer. 2021;12: 7498–7506.
48. Li Y. Lipid Metabolism in Tumor Immunity. Springer Nature; 2021.
49. Jayaraman S, Pazhani J, PriyaVeeraraghavan V, Raj AT, Somasundaram DB, Patil S. PCNA and Ki67: Prognostic proliferation markers for oral cancer. Oral Oncol. 2022;130: 105943.
50. Li Z, Zhang H. Reprogramming of glucose, fatty acid and amino acid metabolism for cancer progression. Cell Mol Life Sci. 2016;73: 377–392.
51. Zhao Q, Lin X, Wang G. Targeting SREBP-1-Mediated Lipogenesis as Potential Strategies for Cancer. Front Oncol. 2022;12: 952371.
52. Johnson AM, Kleczko EK, Nemenoff RA. Eicosanoids in Cancer: New Roles in Immunoregulation. Front Pharmacol. 2020;11: 595498.
53. Bozza PT, Bakker-Abreu I, Navarro-Xavier RA, Bandeira-Melo C. Lipid body function in eicosanoid synthesis: an update. Prostaglandins Leukot Essent Fatty Acids. 2011;85: 205–213.
54. Cruz ALS, Carrossini N, Teixeira LK, Ribeiro-Pinto LF, Bozza PT, Viola JPB. Cell Cycle Progression Regulates Biogenesis and Cellular Localization of Lipid Droplets. Mol Cell Biol. 2019;39. doi:10.1128/MCB.00374-18
55. Tan R, Wang W, Wang S, Wang Z, Sun L, He W, et al. Small GTPase Rab40c associates with lipid droplets and modulates the biogenesis of lipid droplets. PLoS One. 2013;8: e63213.
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May 13, 2023
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Sangamithra.S, Gheena.S, & Pratibha Ramani. (2023). Adipophilin Immunoexpression And Its Pathophysiology In Human Tooth Germ And Ameloblastoma. Journal of Population Therapeutics and Clinical Pharmacology, 30(10), 267–274. https://doi.org/10.47750/jptcp.2023.30.10.031
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