PTEN Plays Dual Roles As a Tumor Suppressor in Osteosarcoma Cells

Abstract

Osteosarcoma (OS) is the most common primary bone cancer, which occurs primarily in children and adolescents. Functional loss of the tumor suppressor PTEN has been demonstrated in bone malignancies including OS. We have recently reported that Pten expression inversely correlates with OS aggressiveness in mouse models. However, the mechanism whereby PTEN exerts its anti-tumor effect remains unknown. In this study, we first examined the expression of PTEN in human OS cell lines including U2OS, MG63 and Saos-2, and found that PTEN expression is reduced as compared to normal human osteoblasts. The downregulation of PTEN also associates with activation of AKT pathway. We then treated previously reported mouse OS tumor cells MOTO-Rank and human OS cell line U2OS with PTEN inhibitor VO-OHpic to investigate how PTEN impacts tumor cell behaviors. Our results showed that PTEN inhibits tumor cell proliferation, migration and invasion, but enhances tumor cell apoptosis. However, PTEN has no effects on tumor cell senescence and chemotaxis. PTEN also fails to induce tumor cells differentiation toward osteoblast lineage. On the other hand, PTEN inhibits tumor associated osteoclast differentiation. Moreover, overexpression of PTEN using gene transfer in U2OS cells inhibits proliferation but increases apoptosis. These findings indicate that PTEN not only targets tumor cells themselves by impacting cell behaviors, but also blocks osteoclast-mediated bone destruction, leading to interruption of the vicious cycle during osteosarcomagenesis. Loss of PTEN may consequently facilitate tumor growth and expansion in bone. Restoration of fully functional PTEN using gene therapy represents a potential approach against OS. J. Cell. Biochem. 118: 2684-2692, 2017. © 2017 Wiley Periodicals, Inc.

Methylation and PTEN activation in dental pulp mesenchymal stem cells promotes osteogenesis and reduces oncogenesis

“…We found that PTEN levels are deregulated in human osteosarcoma. Consistently, Xi et al found that PTEN is reduced in human osteosarcoma cell lines as compared to normal human osteoblasts 41 . Gong et al also found that PTEN is expressed at low level in human osteosarcomas compared to adjacent tissues 42 .…”

Analyzing the disease module associated with osteosarcoma via a network‑ and pathway‑based approach

“…This indicated that our identified OSM was a non-random network. Notably, some of the genes within the OSM, such as small nuclear ribonucleoprotein U11/U12 subunit 25 (SNRNP25) (19,20), cyclin B3 (CCNB3) (21), tumor protein p53 (TP53) (22,23), OS9, endoplasmic reticulum lectin (OS9) (24), and phosphatase and tensin homolog (PTEN) (25), have been reportedly associated with osteosarcoma in previous studies.…”

MiR-214 Attenuates the Osteogenic Effects of Mechanical Loading on Osteoblasts

“…Pten, a tumor suppressor, plays an essential role in bone metabolism and can block osteoclast-mediated bone resorption. It has been reported that the loss of Pten can promote tumor growth and expansion in bone [37]. Recently, Pten was shown to inhibit adipogenesis and promote osteogenesis in both dental pulp mesenchymal stem cells and BMSC [38].…”