Stretching inhibits tumor growth in MMTV-PYMT via a direct mechanical effect

BACKGROUND: Tumor-associated architecture and emerging mechanical properties (forces, pressure, tension, stiffness) affect the growth and invasiveness of cancer cells. Collagen fibers aligned perpendicular to the boundaries of tumors promote local tumor invasiveness in mouse mammary tumor models and are associated with a poor prognosis in human breast cancer. Our previous study revealed that daily gentle stretching (~ 25% strain) for 10 min reduced the growth of P53/PTEN - / - orthotopic mouse mammary tumors by 50%. RESULTS: In this study, we further investigated the mechanism of stretching in a more aggressive MMTV-PYMT (mammary tumor virus- polyomavirus middle T antigen) tumor model in vivo and in vitro and analyzed its impact on collagen reorganization at both the tumor-stromal interface and the tumor microenvironment composition at single-cell level. Stretching reduced the average tumor size by 30-50% in orthotopic (Active and Passive Stretch) and transgenic (Passive Stretch) models. In the orthotopic model, the ratio of parallel vs. perpendicular collagen fibers relative to the tumor boundary was greater in the Stretch group compared with the No Stretch group. Finally, stretching reduced the cell migration of collagen-embedded tumor spheroids in vitro. CONCLUSIONS: These results show that short-duration, moderate-amplitude stretching reduces tumor growth in several different animal models. We also provide evidence that this beneficial effect may be a direct mechanical effect on local matrix properties and tumor cell invasiveness.