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.