DOI: 10.5061/dryad.1rn8pk13r
title: Stretching inhibits tumor growth in MMTV-PYMT via a direct mechanical effect

description: 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.
description: <strong>Berrueta et al tumors collagen signature Data
  092624</strong>: data was collected from images taken by confocal
 second harmonic generation microscopy and analyzed using the CurveAlign
 sofware <strong>Berrueta et al Orthotopic active
 stretch Master file  72623</strong>: data was collected by weekly
 measurements of the tumor using caliper and 3D ultrasound and procceced
 with the VevoLab sofware   <strong>Berrueta et al
 Orthotopic model Passive stretch master file 61223:</strong> data
 was collected by weekly measurements of the tumor using caliper and 3D
 ultrasound and procceced with the VevoLab sofware 
 <strong>Berrueta et al  qPCR data from Orthotopic active
 stretch Master file _Batch 16-18   062323:</strong> data was
 collected by homogenizing the tumors after euthanasia, then extracting RNA
 and running qPCR for gene expression 
 <strong>Berrueta et al  qPCR Orthotopic passive stretch
 Master file Batch   071823</strong>: data was collected by
 homogenizing the tumors after euthanasia, then extracting RNA and running
 qPCR for gene expression  <strong>Berrueta et al 
 Transgenics passive stretch Master file:</strong> data was collected
 weekly using 3D ultrasound and analyzed with the VevoLab
 software  <strong>Berrueta et al  Transgenics
 active stretch Master file:</strong> data was collected weekly using
 3D ultrasound and analyzed with the VevoLab software 
 <strong>Berrueta et al _Spheroids Crown area at day
 3: </strong>data was obtained measuring the area of cell migration
 surrounding each spheroid using the ImageJ software, creating a binary
 image by applying thresholding through: Image/Adjust/Threshold
 <strong>Berrueta et al, Spheroids distance Travelled at day
 3_all data: </strong>Data was obtained from photograph taken from
 the spheroids and then measuring the distance between the spheroid
 boundery and the location of the cell using ImajeJ software The
 calculation of the maximum distance traveled by migratory cells involved
 measuring the distance from the edge of the spheroid to the furthest point
 reached by the migratory cells (the sixteen cells that were at the
 furthest distance from the edge of the spheroid were measured in all
 spheroids) <strong>Berrueta et el,  Spheroids
 single cell migration at day 3</strong> This data was obtained by
 counting the total number of individual cells that migrated away from the
 spheroid 
description: # Stretching inhibits tumor growth in MMTV-PYMT via a direct mechanical
 effect Dataset DOI:
 [10.5061/dryad.1rn8pk13r](https://doi.org/10.5061/dryad.1rn8pk13r) ##
 Description of the data and file structure
 **Berrueta_et_al__qPCR_Orthotopic_passive_stretch_Master_file_Batch___071823.csv** The data include 13 columns: column A is Animal Identification (ID); column B is batch number, column C; is condition: 1=Stretch, 0= No stretch; column D is relative gene expression for collagen 1a1 (Col1a1); column E is relative gene expression for Collagen 5a2 (Col5a2); column F is relative gene expression for Collagen 6a2 (Col6a2); Column G is relative gene expression for Actin Alpha 2, Smooth Muscle (a-SMA), Column H is relative gene expression for Transforming Growth Factor Beta (TGF-b); Column I is relative gene expression for connexin-43; Column J is relative gene expression for Piezo; Column K is relative gene expression for Discoidin Domain Receptor 1 (Ddr1); Column L is relative gene expression for Discoidin Domain Receptor 2 (Ddr2); Column M is relative gene expression for Lysyl Oxidase Like 3 (Loxl3) **Berrueta_et_al__qPCR_data_from_Orthotopic_active_stretch_Master_file__Batch_16-18___062323.csv** The data include 12 columns: column A is Animal Identification (ID); column B is batch number; column C is condition: 1=Stretch, 0= No stretch; column D is relative gene expression for collagen 1a1 (Col1a1); column E is relative gene expression for Collagen 5a2 (Col5a2); column F is relative gene expression for Collagen 6a2 (Col6a2); Column G is relative gene expression for Actin Alpha 2, Smooth Muscle (a-SMA), Column H is relative gene expression for Transforming Growth Factor Beta (TGF-b); Column I is relative gene expression for connexin-43; Column J is relative gene expression for Piezo; Column K is relative gene expression for Discoidin Domain Receptor 1 (Ddr1); Column L is relative gene expression for Discoidin Domain Receptor 2 (Ddr2) **Passive_stretching_amplitude_ultrasound_data.csv** The data include 3 columns: column A is Animal Identification (ID); column B is the amplitude or body displacement during passive stretch, expressed in percentage; column C is the tumor volume by ultrasound expressed in mm^3 **Berrueta_et_al__Transgenic__active_stretch__master_file.csv** The data include 8 columns: column A is Animal Identification (ID); column B is batch number; column C is week number; column D is condition: 1=Stretch, 0= No stretch; column E is animal mass in grams (g); column F is the tumor volume measured by ultrasound and expressed in mm^3; column g is tumor weight in grams (g); column H is the number of lung metastasis **Berrueta_et_al__Transgenics_passive_stretch_Master_file_52423.csv** The data include 6 columns: column A is Animal Identification (ID); column B is batch number; column C is week number; column D is condition: 1=Stretch, 0= No stretch; column E is  the tumor volume measured by ultrasound and expressed in mm^3; column F is tumor weight in grams (g) **Berrueta_et_al__Spheroids_distance_Travelled_at_day_3_all_data.xlsx** The data include 5 columns: column A is the experiment number; column B is group identification, NS=No stretch, S= Stretch; column C is gel number; column D is condition: 0=No stretch, 1= Stretch; column E is distance travelled at day 3 **Berrueta_et_al__Spheroids_Crown_area_at_day_3.csv** The data include 5 columns: column A is the experiment number; column B is group identification, NS=No stretch, S= Stretch; column C is gel number; column D is condition: 0=No stretch, 1= Stretch; column E is Crown area or migration area surrounding the spheroid at day 3  **Berrueta_et_al_tumors_collagen_signature_Data__092624.csv** The data include 4 columns: column A is Animal Identification (ID); column B is animal code for condition: 0=No stretch, 1= Stretch; column C is tumor associated collagen signature 2 (TACS2) expressed in percentage; column D is tumor associated collagen signature 3 (TACS3) expressed in percentage **Berrueta_et_al_Orthotopic_active_stretch_Master_file__72623.csv** The data include 8 columns: column A is Animal Identification (ID); column B is batch number; column C is week number; column D is condition: 1=Stretch, 0= No stretch; column E is animal weight or mass in grams (g); column F is  the tumor volume measured by ultrasound and expressed in mm^3; column F is tumor weight in grams (g); column G is tumor volume measured by caliper (using the formula: 3.14*L*W*W and  averaging  left and right tumors); column H is number of lung metastasis **Berrueta_et_al___Spheroids_single_cell_migration_at_day_3.csv** The data include 5 columns: column A is the experiment number; column B is group identification, NS=No stretch, S= Stretch; column C is gel number; column D is condition: 0=No stretch, 1= Stretch; column E is migration measured per single cell **Berrueta_et_al_Orthotopic_model_Passive_stretch_master_file_61223.csv** The data include 7 columns: column A is Animal Identification (ID); column B is batch number; column C is week number; column D is condition: 1=Stretch, 0= No stretch; column E is  the tumor volume measured by ultrasound and expressed in mm^3; column F is  tumor volume measured by caliper (using the formula: 3.14*L*W*W and  averaging  left and right tumors); column G is tumor weight in grams (g)