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

ABSTRACT: 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

ORGANISM(S): Mus musculus

PROVIDER: GSE316800 | GEO | 2026/02/02

REPOSITORIES: GEO

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Cyclic mechanical stretch-induced gene expression

Project description:With gene expression profiling it was aimed to identify the differentially expressed genes associated with the regulation of the cytoskeleton to investigate the stretch-induced cell alignment mechanism. A whole genome microarray based analysis of the stretch-induced gene expression changes was done. Gene expression was measured at the beginning of the alignment process showing first reoriented cells after 5 h stretching and at the end after 24 h, where nearly all cells are aligned. Cyclic mechanical stretching of cells results in cellular alignment perpendicular to the stretch direction regulating cellular response. This stress response is assumed to be an adaptation mechanism to reduce extensive stretching but also acts as architectural restructuring changing performance and biomechanics of the tissue. Gene expression profiling of control vs. stretched primary human dermal fibroblasts after 5 h and 24 h demonstrated the regulation of differentially expressed genes associated with metabolism, differentiation and morphology.

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Cyclic mechanical stretch-induced gene expression

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Enhanced Collagen Secretion in Epithelial Cancer Cells is associated with L1CAM Deficiency

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Genome wide maps of ELK1 bingding sites in HDFs control and mechanic loading groups.

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Single Cell RNA-sequencing of murine back skin interfollicular epidermis basal cells

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2020-05-18 | GSE146637 | GEO

Induction of muscle-related gene expression in loose connective tissue fibroblasts in response to static tissue stretch

Project description:Current knowledge of mechanically-induced regulation of gene expression in fibroblast is mostly based on experiments using prolonged cyclical stretching of either cultured cells or load-bearing connective tissues such as tendons and ligaments. In this study, we have examined the effect of static tissue stretch on fibroblasts within loose connective tissue using in vivo and ex vivo models. In an in vivo trunk side bending model, one side of the trunk of the mouse was stretched while the other side was shortened under anesthesia for 90 minutes. In the ex vivo method, whole subcutaneous tissue explants (including skin, subcutaneous muscle and subcutaneous tissue) from both sides of the trunk were incubated ex vivo either stretched or not stretched (shortened) for 24 hours. Tissue stretch or shortening was followed by immediate dissection of the loose connective tissue layer on both sides of the trunk, RNA extraction and gene expression analysis using Affymetrix mouse gene arrays. In both in vivo and ex vivo experiments, a large cluster of genes related to skeletal muscle function and carbohydrate metabolism was up-regulated in the stretched, compared with the shortened, connective tissue samples. However, there were few differentially expressed matrix-related genes, and in particular no change in collagen genes. Immunohistochemical staining for myosin after tissue stretch for 24 hours ex vivo showed increased myosin immunoreactivity in fibroblasts within the stretched compared with the shortened tissue samples. These results suggest that dynamic modulation of muscle-related gene expression is a normal physiological response of loose connective tissue fibroblasts to changes in tissue length.. Keywords: response to mechanical stretch Within animal stretched vs shortened (randomized): 7 animals in vivo and 4 ex vivo.

2011-05-08 | E-GEOD-11371 | biostudies-arrayexpress

Mechanical stretch exacerbates imiquimod-induced dermatitis associated with increased IL-1β and IL-6 production.

Project description:Psoriasis vulgaris is a chronic inflammatory skin disease which tends to affect the extensor surface of the body. IL-17A and IL-23 antagonists are currently the main and powerful therapeutic choices but the skin areas which are subject to stretching, namely knees, elbows and the lower back, are often reluctant to treatments. ; Hence, we hypothesize that stretching has a dominant effect on psoriasis development. First, we found that, in imiquimod-treated psoriasis-like mouse model, mechanical stretch promotes a significant increase in clinical severity, epidermal thickness, and inflammatory cell infiltration of psoriasis. Transcriptomics profiling revealed that Il6 and Il1b genes are significantly upregulated and play a major role in the activation and recruitment of neutrophils, macrophages, and T cells in stretching group. Upstream analysis further identifies NF-κB as a critical transcription factor to drive pro-inflammatory cytokine expression during stretch application. Immunofluorescence staining confirmed the increased expression of IL-1β and IL-6. In summary, our findings uncover that the mechanical biology contributes to psoriasis progression mainly through enhancing the production of IL-1β and IL-6.

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Stretch growth does not alter gene expression

Project description:Differentiated PC12 cells were magnetically labeled with magnetic nanoparticles (MNP). External magnetic fields were used to mechanically stretch the MNP-labeled neurites. We found that mechanical stretching of the neurites induces mass addition and neurite elongation. We performed RNAseq of MNP-labelled cells in stretched versus non-stretched conditions and we did not found gene expression dysregulation, confirming that the two conditions were identical and excluding cytotoxicity or involvement of nuclear mechanotransdution. Indeed, local mechanisms triggered by the stretching of the MNP-labelled neurite would be responsible for neurite elongation.

2018-06-08 | GSE115474 | GEO

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