Evaluating the role of PTH in promotion of chondrosarcoma cell proliferation and invasion by inhibiting primary cilia expression.

Abstract

Chondrosarcoma is characterized by secretion of a cartilage-like matrix, with high proliferation ability and metastatic potential. Previous studies have shown that parathyroid hormone-related protein (PTHrP) has a close relationship with various tumor types. The objectives of this study were to research the function played by PTHrP in human chondrosarcoma, especially targeting cell proliferation and invasion, and to search for the potential interaction between PTHrP and primary cilia in tumorigenesis. Surgical resection tissues and the human chondrosarcoma cell line SW1353 were used in the scientific research. Cells were stimulated with an optimum concentration of recombinant PTH (1-84), and siRNA was used to interfere with internal PTHrP. Cell proliferation and invasion assays were applied, including MTS-8 cell proliferation assay, Western blot, RT-PCR, Transwell invasion assay, and immunohistochemistry and immunofluorescence assays. A high level of PTHrP expression was found in human chondrosarcoma tissues, and recombinant PTH exhibited positive promotion in tumor cell proliferation and invasion. In the meantime, PTHrP could inhibit the assembly of primary cilia and regulate downstream gene expression. These findings indicate that PTHrP can regulate tumor cell proliferation and invasion ability, possibly through suppression of primary cilia assembly. Thus, restricting PTHrP over-expression is a feasible potential therapeutic method for chondrosarcoma.

• Authors: Wei Xiang, Ting Jiang, Fengjing Guo, Tao Xu, Chen Gong, Peng Cheng, Libo Zhao, Weiting Cheng, Kai Xu
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 15 Issue 11 Pg. 19816-31 (Oct 31 2014) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 25365173 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hedgehog Proteins
• Parathyroid Hormone
• Parathyroid Hormone-Related Protein
• RNA, Small Interfering
• Recombinant Proteins
• MMP2 protein, human
• Matrix Metalloproteinase 2
• MMP9 protein, human
• Matrix Metalloproteinase 9

Topics

• Bone Neoplasms (metabolism, pathology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Chondrosarcoma (metabolism, pathology)
• Cilia (metabolism)
• Hedgehog Proteins (metabolism)
• Humans
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Parathyroid Hormone (genetics, metabolism, pharmacology)
• Parathyroid Hormone-Related Protein (antagonists & inhibitors, genetics, metabolism)
• RNA Interference
• RNA, Small Interfering (metabolism)
• Recombinant Proteins (biosynthesis, genetics, pharmacology)
• Signal Transduction