Stretching attenuates tumor growth and improves tumor-associated collagen signatures in mouse orthotopic PyMT cancer model

Abstract

Abstract Both mechanical forces and tumor-associated stroma architecture have been demonstrated to impact the growth and invasiveness of cancer cells. Tumor associated collagen signatures (TACS) aligned perpendicular to the boundary of tumors promote local tumor invasiveness in mouse mammary tumor models and are associated with a poor prognosis in humans breast cancer. A previous study showed that daily gentle stretching for 10 minutes reduced the growth of p53/PTEN-/- orthotopic mouse mammary tumors by 50%. In this study, we hypothesized that a similar stretching intervention would reduce both tumor growth and perpendicular collagen fibers at the tumor boundary. We tested this in a more aggressive orthotopic MMTV-PyMT mammary tumor model allowing us to test the effect of stretching on metastases. Stretching reduced average tumor volume by 40% and 33%, measured by caliper and ultrasound, respectively (p < .001). There was no significant effect of stretching on the number of lung metastases. The percentages of collagen fibers oriented parallel (TACS2) and perpendicular (TACS3) to the tumor were respectively higher and lower in the stretch group, resulting in an increased TACS 2/TACS 3 ratio in stretch vs. no-stretch groups (p = .04). These results suggest that stretching could modify the tumor-surrounding matrix potentially impacting disease outcome.