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.
Highlights
Chondrosarcoma, as a type of tumor producing a cartilage-like matrix, is one of the most common primary malignant bone tumors
Through immunohistochemical staining, we found that human chondrosarcoma tissues apparently expressed an elevated level of Parathyroid hormone-related protein (PTHrP), compared with adjacent tissues (Figure 1)
Previous study confirmed that an Ihh/PTHrP negative loop exists in normal cartilage growth and the differentiation process
Summary
Chondrosarcoma, as a type of tumor producing a cartilage-like matrix, is one of the most common primary malignant bone tumors. This tumor generally occurs in patients aged more than 20 years [1,2,3], and the 10-year survival rate ranges from 29% to 83%, based on the tumor’s degree of differentiation [4,5]. PTHrP was found to be regulated by the expression of Hedgehog (Hh) signaling pathway downstream transcription zinc finger protein GLI2 and to suppress the expression of effective Ihh protein in turn [7,10] This feedback loop can control cartilage cells’ maturation and postpone the process of endochondral ossification, helping to maintain bone structure and function [12]
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