Fibroblasts regulate variable aggressiveness of syndromic keratocystic and non-syndromic odontogenic tumors.

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.

• Authors: Y-Y Hong, F-Y Yu, J-F Qu, F Chen, T-J Li
• Journal: Journal of dental research (J Dent Res) Vol. 93 Issue 9 Pg. 904-10 (Sep 2014) ISSN: 1544-0591 [Electronic] United States
• PMID: 24972872 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © International & American Associations for Dental Research.

Chemical References

• Biomarkers
• Collagen Type I
• Collagen Type I, alpha 1 Chain
• Core Binding Factor Alpha 1 Subunit
• Isoenzymes
• Osteoprotegerin
• RANK Ligand
• RUNX2 protein, human
• TNFRSF11B protein, human
• TNFSF11 protein, human
• Osteocalcin
• Osteopontin
• Cyclooxygenase 2
• PTGS2 protein, human
• Alkaline Phosphatase
• Acid Phosphatase
• Tartrate-Resistant Acid Phosphatase

Topics

• Acid Phosphatase (analysis)
• Alkaline Phosphatase (analysis)
• Basal Cell Nevus Syndrome (pathology)
• Biomarkers (analysis)
• Cell Culture Techniques
• Cell Differentiation (physiology)
• Cell Line
• Cell Lineage (physiology)
• Cell Nucleus (pathology)
• Cell Proliferation
• Collagen Type I (analysis)
• Collagen Type I, alpha 1 Chain
• Core Binding Factor Alpha 1 Subunit (analysis)
• Cyclooxygenase 2 (analysis)
• Fibroblasts (physiology)
• Humans
• Isoenzymes (analysis)
• Jaw Neoplasms (pathology)
• Odontogenic Tumors (pathology)
• Osteoblasts (physiology)
• Osteocalcin (analysis)
• Osteoclasts (physiology)
• Osteogenesis (physiology)
• Osteopontin (analysis)
• Osteoprotegerin (analysis)
• RANK Ligand (analysis)
• Tartrate-Resistant Acid Phosphatase