Fibroblasts Regulate Variable Aggressiveness of Syndromic Keratocystic and Non-syndromic Odontogenic Tumors

Overview

Journal J Dent Res

Specialty Dentistry

Date 2014 Jun 29

PMID 24972872

Citations 7

Authors

Y-Y Hong

F-Y Yu

J-F Qu

F Chen

T-J Li

Affiliations

Soon will be listed here.

Abstract

Unlabelled: Keratocystic odontogenic tumors (KCOTs) are jaw lesions that can be either sporadic or associated with nevoid basal cell carcinoma syndrome, which typically occurs as multiple, aggressive lesions that can lead to large areas of bone destruction and resorption and cause major impairment and even jaw fracture. To clarify the role of fibroblasts in the aggressivness of syndromic (S-) as compared with non-syndromic (NS-) KCOTs, we assessed fibroblasts derived from 16 S- and NS-KCOTs for differences in cell proliferation, multilineage differentiation potential, alkaline phosphatase activity, and osteoclastogenic potential. S-KCOT fibroblasts had proliferative and osteoclastogenic capacity higher than those from NS-KCOTs, as evidenced by higher numbers of tartrate-resistant acid-phosphatase-positive multinuclear cells, expression of cyclooxygenase 2, and ratio of receptor activator of nuclear factor-kappa B ligand to osteoprotegerin. The osteogenic potential was higher for S- than for NS-KCOT fibroblasts and was associated with lower mRNA expression of runt-related transcription factor 2, collagen type I α1, osteocalcin, and osteopontin as well as reduced alkaline phosphatase activity. These results suggest that the distinct characteristics of fibroblasts in KCOTs are responsible for the greater aggressiveness observed in the syndromic subtype.

Abbreviations: AP, alkaline phosphatase; CK, cytokeratin; COL1A1, collagen type I α1; COX-2, cyclooxygenase-2; GM-CSF, granulocyte-macrophage colony-stimulating factor; IL-1α, interleukin 1α; KCOT, keratocystic odontogenic tumor; NBCCS, nevoid basal cell carcinoma syndrome; NS-KCOT, non-syndrome-associated KCOT; OCN, osteocalcin; OPG, osteoprotegerin; OPN, osteopontin; RANKL, receptor activator of nuclear factor-kappa B ligand; Runx2, runt-related transcription factor 2; S-KCOT, syndrome-associated KCOT; TAF, tumor-associated fibroblast; and TRAP, tartrate-resistant acid phosphatase.

Citing Articles

Immunohistochemical Analysis of Dentigerous Cysts and Odontogenic Keratocysts Associated with Impacted Third Molars-A Systematic Review.

Almeida L, Loyd D, Boettcher D, Kraft O, Zammuto S Diagnostics (Basel). 2024; 14(12).

PMID: 38928661 PMC: 11202764. DOI: 10.3390/diagnostics14121246.

A Comparative Immunohistochemical Expression of TRAP in Odontogenic Cysts.

Kadeh H, Saravani S, Jamshidi A Iran J Otorhinolaryngol. 2023; 35(131):295-301.

PMID: 38074480 PMC: 10701248. DOI: 10.22038/IJORL.2023.63350.3169.

Identification of Immune Infiltration in Odontogenic Keratocyst by Integrated Bioinformatics Analysis.

Zhong N, Li S, Man Q, Liu B BMC Oral Health. 2023; 23(1):454.

PMID: 37415178 PMC: 10324234. DOI: 10.1186/s12903-023-03175-9.

Expression of Matrix Metalloproteinases 7 and 9, Desmin, Alpha-Smooth Muscle Actin and Caldesmon, in Odontogenic Keratocyst Associated with NBCCS, Recurrent and Sporadic Keratocysts.

Loreto C, Polizzi A, Filetti V, Pannone G, Nunes Dos Santos J, Venezia P Biomolecules. 2022; 12(6).

PMID: 35740900 PMC: 9221122. DOI: 10.3390/biom12060775.

A CREB1-miR-181a-5p loop regulates the pathophysiologic features of bone marrow stromal cells in fibrous dysplasia of bone.

Fu Y, Xin Z, Ling Z, Xie H, Xiao T, Shen X Mol Med. 2021; 27(1):81.

PMID: 34294046 PMC: 8296714. DOI: 10.1186/s10020-021-00341-z.

References

Enomoto H, Shiojiri S, Hoshi K, Furuichi T, Fukuyama R, Yoshida C . Induction of osteoclast differentiation by Runx2 through receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin regulation and partial rescue of osteoclastogenesis in Runx2-/- mice by RANKL transgene. J Biol Chem. 2003; 278(26):23971-7. DOI: 10.1074/jbc.M302457200. View

Li T . The odontogenic keratocyst: a cyst, or a cystic neoplasm?. J Dent Res. 2011; 90(2):133-42. DOI: 10.1177/0022034510379016. View

Hahn H, Wicking C, Zaphiropoulous P, Gailani M, Shanley S, Chidambaram A . Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell. 1996; 85(6):841-51. DOI: 10.1016/s0092-8674(00)81268-4. View

Cheng M, Yang H, Chen T, Lee O . Isolation and characterization of multipotent stem cells from human cruciate ligaments. Cell Prolif. 2009; 42(4):448-60. PMC: 6495698. DOI: 10.1111/j.1365-2184.2009.00611.x. View

Zeisberg M, Strutz F, Muller G . Role of fibroblast activation in inducing interstitial fibrosis. J Nephrol. 2000; 13 Suppl 3:S111-20. View

Hakim S, Kosmehl H, Sieg P, Trenkle T, Jacobsen H, Benedek G . Altered expression of cell-cell adhesion molecules β-catenin/E-cadherin and related Wnt-signaling pathway in sporadic and syndromal keratocystic odontogenic tumors. Clin Oral Investig. 2010; 15(3):321-8. DOI: 10.1007/s00784-010-0388-8. View

Barreto D, Gomez R, Bale A, Boson W, De Marco L . PTCH gene mutations in odontogenic keratocysts. J Dent Res. 2000; 79(6):1418-22. DOI: 10.1177/00220345000790061101. View

Koontongkaew S, Amornphimoltham P, Monthanpisut P, Saensuk T, Leelakriangsak M . Fibroblasts and extracellular matrix differently modulate MMP activation by primary and metastatic head and neck cancer cells. Med Oncol. 2011; 29(2):690-703. DOI: 10.1007/s12032-011-9871-6. View

Li T, BROWNE R, Matthews J . Quantification of PCNA+ cells within odontogenic jaw cyst epithelium. J Oral Pathol Med. 1994; 23(4):184-9. DOI: 10.1111/j.1600-0714.1994.tb01110.x. View

10.

Pan S, Dong Q, Sun L, Li T . Mechanisms of inactivation of PTCH1 gene in nevoid basal cell carcinoma syndrome: modification of the two-hit hypothesis. Clin Cancer Res. 2010; 16(2):442-50. DOI: 10.1158/1078-0432.CCR-09-2574. View

11.

Nonaka C, Cavalcante R, Nogueira R, de Souza L, Pereira Pinto L . Immunohistochemical analysis of bone resorption regulators (RANKL and OPG), angiogenic index, and myofibroblasts in syndrome and non-syndrome odontogenic keratocysts. Arch Oral Biol. 2011; 57(3):230-7. DOI: 10.1016/j.archoralbio.2011.08.002. View

12.

Kimonis V, Goldstein A, Pastakia B, Yang M, Kase R, DiGiovanna J . Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Am J Med Genet. 1997; 69(3):299-308. View

13.

Amorim R, Godoy G, Galvao H, Souza L, Freitas R . Immunohistochemical assessment of extracellular matrix components in syndrome and non-syndrome odontogenic keratocysts. Oral Dis. 2004; 10(5):265-70. DOI: 10.1111/j.1601-0825.2004.01023.x. View

14.

Daly A, McIlreavey L, Irwin C . Regulation of HGF and SDF-1 expression by oral fibroblasts--implications for invasion of oral cancer. Oral Oncol. 2007; 44(7):646-51. DOI: 10.1016/j.oraloncology.2007.08.012. View

15.

Levanat S, GORLIN R, Fallet S, Johnson D, Fantasia J, Bale A . A two-hit model for developmental defects in Gorlin syndrome. Nat Genet. 1996; 12(1):85-7. DOI: 10.1038/ng0196-85. View

16.

Ba K, Li X, Wang H, Liu Y, Zheng G, Yang Z . Correlation between imaging features and epithelial cell proliferation in keratocystic odontogenic tumour. Dentomaxillofac Radiol. 2010; 39(6):368-74. PMC: 3520243. DOI: 10.1259/dmfr/27538271. View

17.

Gorlin R . Nevoid basal cell carcinoma (Gorlin) syndrome. Genet Med. 2004; 6(6):530-9. DOI: 10.1097/01.gim.0000144188.15902.c4. View

18.

Katase N, Nagatsuka H, Tsujigiwa H, Gunduz M, Tamamura R, Pwint H . Analysis of the neoplastic nature and biological potential of sporadic and nevoid basal cell carcinoma syndrome-associated keratocystic odontogenic tumor. J Oral Pathol Med. 2007; 36(9):550-4. DOI: 10.1111/j.1600-0714.2007.00578.x. View

19.

Wang H, Li T . The growth and osteoclastogenic effects of fibroblasts isolated from keratocystic odontogenic tumor. Oral Dis. 2012; 19(2):162-8. DOI: 10.1111/j.1601-0825.2012.01966.x. View

20.

Brabek J, Mierke C, Rosel D, Vesely P, Fabry B . The role of the tissue microenvironment in the regulation of cancer cell motility and invasion. Cell Commun Signal. 2010; 8:22. PMC: 2941745. DOI: 10.1186/1478-811X-8-22. View