Therapeutic Insights into Low-intensity Vibration for Generating Induced Tumor-Suppressive Cells and Modulating the Bone Microenvironment
Xue Xiong,
Qingji Huo,
Changpeng Cui,
Uma K. Aryal,
BonHeon Ku,
Chin-Suk Hong,
HeeChang Lim,
Jing Liu,
Andy Chen,
William R. Thompson,
Bai-Yan Li,
Xue-Lian Li,
Hiroki Yokota
Affiliations
Xue Xiong
Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China; Department of Biomedical Engineering, Purdue University in Indianapolis, Indianapolis, IN 46202, USA; Department of Physics and Astronomy, Purdue University, West Lafayette, IN 47907, USA
Qingji Huo
Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China; Department of Biomedical Engineering, Purdue University in Indianapolis, Indianapolis, IN 46202, USA
Changpeng Cui
Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China; Department of Biomedical Engineering, Purdue University in Indianapolis, Indianapolis, IN 46202, USA
Uma K. Aryal
Department of Comparative Pathobiology, Purdue University, West Lafayette, IN 47907, USA
BonHeon Ku
School of Mechanical Engineering, Pusan National University, Busan 46241, Republic of Korea
Chin-Suk Hong
Department of Mechanical Engineering, Ulsan College, Ulsan 44022, Republic of Korea
HeeChang Lim
School of Mechanical Engineering, Pusan National University, Busan 46241, Republic of Korea
Jing Liu
Department of Physics and Astronomy, Purdue University, West Lafayette, IN 47907, USA; Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Andy Chen
Department of Medical Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
William R. Thompson
Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Physical Therapy, Indiana University, Indianapolis, IN 46202, USA
Bai-Yan Li
Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China
Xue-Lian Li
Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China; Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin 150086, China; Corresponding authors.
Hiroki Yokota
Department of Biomedical Engineering, Purdue University in Indianapolis, Indianapolis, IN 46202, USA; Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Corresponding authors.
Bone frequently serves as a metastatic site for breast and prostate cancers. Given the potential of low-intensity vibration (LIV) to increase bone health and reduce cancer risk, this study investigated the impact of LIV on cancer cells, as well as noncancer cells such as lymphocytes and peripheral blood mononuclear cells (PBMCs). The results revealed that LIV exposure not only suppressed cancer cell migration but also triggered the generation of induced tumor-suppressing (iTS) cells. Conditioned medium (CM) derived from LIV-treated PBMCs shrank freshly isolated breast and prostate cancer tissues, and when CM was combined with a chemotherapeutic agent, additional antitumor effects were observed. Notably, iTS cell-derived CM hindered the maturation of the receptor activator of nuclear factor-kappa B ligand (RANKL)-stimulated bone-resorbing osteoclasts while promoting the differentiation of bone-forming osteoblasts. Intriguingly, the anticancer effects induced by LIV were replicated by simply shaking a cell-containing tube with a regular tube shaker. Using mass spectrometry-based proteomics, this study revealed enrichment of tumor-suppressing proteins, including enolase 1, moesin (MSN), and aldolase A (ALDOA), which are commonly found in oncogene-activated iTS cells, in LIV-induced CM. Sad1 and UNC-84 domain containing 1 (SUN1), a core component of the linker of the nucleoskeleton and cytoskeleton (LINC) complex, exhibited heightened expression, notably enhancing the response of lymphocytes to LIV. An ex vivo bone cancer model further demonstrated the potent anticancer effects of lymphocyte-derived CM. In conclusion, this study underscores the pivotal role of LIV in preventing bone loss in the tumor microenvironment.
