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The downregulation of IGFBP3 by TGF-β signaling in oral cancer contributes to the osteoclast differentiation
- Source :
- Biochemical and Biophysical Research Communications. 534:381-386
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Oral squamous cell carcinoma (OSCC) frequently invades nearby bone and bone involvement determines the prognosis of patients. Growth factors, stored in the bone matrix and released during bone destruction, are known as key components in the bone-tumor interaction. However, the coordination of growth factor signals and the precise mechanism of bone destruction in oral cancer are still unclear. In the study, we investigated the differential cytokine expression profile of oral cancer cells by TGF-β treatment and the function of altered expression of cytokines on the osteoclast differentiation. We established TGFBR2-knockdown cells using small hairpin RNA. TGF-β was treated to both TGFBR2 expressing and knockdown cells and the culture supernatants were analyzed using a cytokine array kit. We found that the TGF-β inhibited IGFBP3 level and enhanced MMP9 level. We confirmed this regulation of IGFBP3 and MMP9 by TGF-β using ELISA and zymography, respectively. IGFBP3 is known as to modulate the bioavailability of IGF1, which is abundant in the bone microenvironment and regulates osteoclast differentiation. Therefore, we further analyzed the function of IGFBP3 on osteoclastogenesis. Although IGFBP3 increased the viability of murine bone marrow macrophages, the osteoclast differentiation of these cells was blocked by IGFBP3 in a dose-dependent manner. These results revealed a novel pathway for the regulation of osteoclastogenesis by oral cancer cells, which may be a new therapeutic target for osteolysis induced by oral cancer infiltrating into the bone.
- Subjects :
- Male
0301 basic medicine
Osteolysis
medicine.medical_treatment
Biophysics
Down-Regulation
Osteoclasts
Biochemistry
Small hairpin RNA
Mice
03 medical and health sciences
0302 clinical medicine
Osteogenesis
Transforming Growth Factor beta
Osteoclast
Cell Line, Tumor
medicine
Animals
Humans
Insulin-Like Growth Factor I
Molecular Biology
Mice, Inbred ICR
Squamous Cell Carcinoma of Head and Neck
Chemistry
Macrophages
Growth factor
RANK Ligand
Osteoprotegerin
Receptor, Transforming Growth Factor-beta Type II
Cancer
Cell Differentiation
Cell Biology
medicine.disease
Insulin-Like Growth Factor Binding Protein 3
030104 developmental biology
Cytokine
medicine.anatomical_structure
Matrix Metalloproteinase 9
Gene Knockdown Techniques
030220 oncology & carcinogenesis
Cancer cell
Cancer research
Mouth Neoplasms
Bone marrow
Signal Transduction
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 534
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....283523664ef3221367bba3ada3c8e56b