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Research Paper|Volume 13, Issue 6|pp 8989—9010

Primary cilia regulate gastric cancer-induced bone loss via cilia/Wnt/β-catenin signaling pathway

Jie Xu1, Xiaoyan Deng1, Xiangmei Wu2, Huifang Zhu1, Yinghua Zhu3, Jie Liu1, Qian Chen1, Chengfu Yuan4, Geli Liu1, Changdong Wang1
  • 1Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
  • 2Department of Physiology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
  • 3Department of Pre-Hospital Emergency, Chongqing Emergency Medical Center, Central Hospital of Chongqing University, Chongqing 400014, China
  • 4College of Medical Science, China Three Gorges University, Yichang 443002, Hubei, China
* Equal contribution
Received: September 19, 2020Accepted: February 8, 2021Published: March 9, 2021
https://doi.org/10.18632/aging.202734

Copyright: © 2021 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Cancer-associated bone disease is a frequent occurrence in cancer patients and is associated with pain, bone fragility, loss, and fractures. However, whether primary or non-bone metastatic gastric cancer induces bone loss remains unclear. Here, we collected clinical evidence of bone loss by analyzing serum and X-rays of 25 non-bone metastatic gastric cancer patients. In addition, C57BL mice were injected with the human gastric cancer cell line HGC27 and its effect on bone mass was analyzed by Micro-CT, immunoblotting, and immunohistochemistry. Furthermore, the degree of the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) co-cultured with HGC-27 or SGC-7901 cells was analyzed by colony-formation assay, alizarin red staining, immunofluorescence, qPCR, immunoblotting, and alkaline phosphatase activity assay. These indicated that gastric cancer could damage bone tissue before the occurrence of bone metastases. We also found that cilia formation of MSCs was increased in the presence of HGC27 cells, which was associated with abnormal activation of the Wnt/β-catenin pathway. Expression of DKK1 inhibited the Wnt/β-catenin signaling pathway and partially rescued osteogenic differentiation of MSCs. In summary, our results suggest that gastric cancer cells might cause bone damage prior to the occurrence of bone metastasis via cilia-dependent activation of the Wnt/β-catenin signaling pathway.