ABSTRACT
Keratocystic odontogenic tumors (KCOT) are benign, locally aggressive intraosseous tumors of odontogenic origin. KCOT have a higher stromal microvessel density (MVD) than dentigerous cysts (DC) and normal oral mucosa. To identify genes in the stroma of KCOT involved in tumor development and progression, RNA sequencing (RNA-Seq) was performed using samples from KCOT and primary stromal fibroblasts isolated from gingival tissues. Seven candidate genes that possess a function potentially related to KCOT progression were selected and their expression levels were confirmed by quantitative PCR, immunohistochemistry and enzyme-linked immunosorbent assay. Expression of lysyl oxidase-like 4 (LOXL4), the only candidate gene that encodes a secreted protein, was enhanced at both the mRNA and protein levels in KCOT stromal tissues and primary KCOT stromal fibroblasts compared to control tissues and primary fibroblasts (P<0.05). In vitro, high expression of LOXL4 could enhance proliferation and migration of the human umbilical vein endothelial cells (HUVECs). There was a significant, positive correlation between LOXL4 protein expression and MVD in stroma of KCOT and control tissues (r=0.882). These data suggest that abnormal expression of LOXL4 of KCOT may enhance angiogenesis in KCOT, which may help to promote the locally aggressive biological behavior of KCOT.
Subject(s)
Amino Acid Oxidoreductases/genetics , Odontogenic Tumors/enzymology , Adult , Cell Movement/genetics , Cell Proliferation , Dentigerous Cyst/enzymology , Dentigerous Cyst/pathology , Disease Progression , Female , Fibroblasts/pathology , Gene Expression Regulation, Enzymologic/genetics , Gingiva/pathology , Human Umbilical Vein Endothelial Cells/pathology , Humans , Male , Microvessels/pathology , Neovascularization, Pathologic/genetics , Odontogenic Tumors/blood supply , Odontogenic Tumors/pathology , Protein-Lysine 6-Oxidase , Sequence Analysis, RNA , Stromal Cells/pathology , Young AdultABSTRACT
OBJECTIVE: To investigate the expression of parafibromin in osteosarcoma of the jaws (JOS) and to explore its effects on tumorigenesis and progression. METHODS: The expression of parafibromin was studied in 47 JOS and 11 ossifying fibroma of the jaws (JOF) by immunohistochemically staining. RESULTS: In JOS, the high, medium and low levels of parafibromin expression were detected in 48.9% (23/47), 40.4% (19/47) ,and 10.7% (5/47) of the cases, respectively; correspondingly, the different expressions were seen in 90.9% (10/11), 9.1% (1/11), and 0.0% (0) JOF cases respectively. The difference between JOS and JOF groups was significantly different (U=147.5,P=0.012). In highly differentiated JOS, the expression of parafibromin was significantly higher than that in the conventional JOS (U=71.0,P=0.021) but there were no statistically correlations between the expression of parafibromin and clinical-pathological parameters of JOS (P>0.05). CONCLUSION: It is possible that the down-regulation of parafibromin may be associated with the differentiation and malignant degree of JOS.
