Related Experiment Video
Updated: Dec 13, 2025
The Soft Agar Colony Formation Assay
Published on: October 27, 2014
Mechanical stimulations can inhibit local and remote tumor progression by downregulating WISP1
Shengzhi Liu1, Di Wu1,2, Xun Sun1,2
1Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN, USA.
Abstract:
Mechanical stimulations can prevent bone loss, but their effects on the tumor-invaded bone or solid tumors are elusive. Here, we evaluated the effect of knee loading, dynamic loads applied to the knee, on metastasized bone and mammary tumors. In a mouse model, tumor cells were inoculated to the mammary fat pad or the proximal tibia. Daily knee loading was then applied and metabolic changes were monitored mainly through urine. Urine samples were also collected from human subjects before and after step aerobics. The result showed that knee loading inhibited tumor progression in the loaded tibia. Notably, it also reduced remotely the growth of mammary tumors. In the urine, an altered level of cholesterol was observed with an increase in calcitriol, which is synthesized from a cholesterol derivative. In urinary proteins, knee loading in mice and step aerobics in humans markedly reduced WNT1-inducible signaling pathway protein 1, WISP1, which leads to poor survival among patients with breast cancer. In the ex vivo breast cancer tissue assay, WISP1 promoted the growth of cancer fragments and upregulated tumor-promoting genes, such as Runx2, MMP9, and Snail. Collectively, the present preclinical and human study demonstrated that mechanical stimulations, such as knee loading and step aerobics, altered urinary metabolism and downregulated WISP1. The study supports the benefit of mechanical stimulations for locally and remotely suppressing tumor progression. It also indicated the role of WISP1 downregulation as a potential mechanism of loading-driven tumor suppression.
Insights
Mechanical knee loading and step aerobics inhibit tumor growth locally and remotely. This is linked to reduced WNT1-inducible signaling pathway protein 1 (WISP1) and altered urinary metabolism, suggesting mechanical stimulation as a cancer therapy.
Area of Science:
- Biomedical Engineering
- Oncology
- Metabolomics
Background:
- Mechanical stimulation is known to prevent bone loss.
- The impact of mechanical loading on bone metastasis and solid tumors remains unclear.
- Understanding these effects is crucial for developing novel cancer therapies.
Purpose of the Study:
- To investigate the effects of knee loading on bone metastasis and mammary tumors in a preclinical model.
- To explore the metabolic changes associated with mechanical stimulation in mice and humans.
- To identify potential molecular mechanisms underlying mechanical stimulation-induced tumor suppression.
Main Methods:
- A mouse model with inoculated tumor cells in the tibia and mammary fat pad.
- Daily knee loading applied to mice, with metabolic monitoring via urine analysis.
- Collection and analysis of urine samples from human subjects before and after step aerobics.
- Ex vivo analysis of breast cancer tissue to assess the role of WISP1.
Main Results:
- Knee loading inhibited tumor progression in the loaded tibia and reduced remote mammary tumor growth.
- Mechanical stimulation altered urinary cholesterol levels and increased calcitriol.
- Both mouse knee loading and human step aerobics significantly reduced urinary WNT1-inducible signaling pathway protein 1 (WISP1).
- WISP1 was found to promote breast cancer fragment growth and upregulate tumor-promoting genes in vitro.
Conclusions:
- Mechanical stimulations, including knee loading and step aerobics, can suppress tumor progression both locally and remotely.
- Downregulation of WISP1 is a potential mechanism for mechanical stimulation-driven tumor suppression.
- Altered urinary metabolism, including changes in cholesterol and calcitriol, is associated with mechanical loading.
Related Concept Videos
02:54Canonical Wnt Signaling Pathway
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
02:23Abnormal Proliferation
01:41Non-Canonical Wnt Signaling Pathways
01:20The JAK-STAT Signaling Pathway
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...