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.

The primary cilium as a signaling nexus for growth plate function and subsequent skeletal development

“…Treatment with Hh pathway inhibitor 4 (HPI‐4) decreases both Ift88 and PTHrP protein and mRNA expression . Additionally, Ift88 expression and cilium incidence increase when the PTHrP gene is silenced . These studies suggest the cilium is directly affected by PTHrP, but the direct effects of cilium disruption on PTHrP signaling are yet to be explored.…”

The association of Minerals Intake in Three Meals with Cancer and All-Cause Mortality: The U.S. National Health and Nutrition Examination Survey, 2003-2014

“…One underlying possible explanation response for the results in this study is that higher calcium intake in the evening might down-regulated the circulating of parathyroid hormone (PTH) [26]. It has been documented that PTH is a tumor promoter acting as a co-mitogen and anti-apoptotic factor, which may further stimulate cell proliferation and intensively suppress apoptosis of cells [27,28]. The circadian rhythm of PTH showed a biphasic rhythm with a small but signi cant increase in the late afternoon and a larger, broader increase in the late evening into the early morning with a peak [29].…”

Primary cilia: Versatile regulator in cartilage development

“…PTH, another active growth factor, plays an important role in regulating cartilage development. Regulating PTH signalling can affect the malignant properties of chondrosarcoma by affecting primary cilia expression and function . These results may provide new ideas for exploring the pathogenetic mechanisms of cartilage tumorigenesis and the potential treatments for cartilage tumours.…”