Ascites-induced compression alters the peritoneal microenvironment and promotes metastatic success in ovarian cancer.
Animals
Anisotropy
Ascites
/ pathology
Cell Adhesion
Cell Line, Tumor
Collagen
/ metabolism
Epithelium
/ pathology
Female
Humans
Mice, Inbred C57BL
Mitochondria
/ pathology
Models, Biological
Nanotubes
/ chemistry
Neoplasm Metastasis
Ovarian Neoplasms
/ pathology
Peritoneum
/ pathology
Tumor Microenvironment
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
17 07 2020
17 07 2020
Historique:
received:
23
02
2020
accepted:
26
06
2020
entrez:
19
7
2020
pubmed:
19
7
2020
medline:
15
12
2020
Statut:
epublish
Résumé
The majority of women with recurrent ovarian cancer (OvCa) develop malignant ascites with volumes that can reach > 2 L. The resulting elevation in intraperitoneal pressure (IPP), from normal values of 5 mmHg to as high as 22 mmHg, causes striking changes in the loading environment in the peritoneal cavity. The effect of ascites-induced changes in IPP on OvCa progression is largely unknown. Herein we model the functional consequences of ascites-induced compression on ovarian tumor cells and components of the peritoneal microenvironment using a panel of in vitro, ex vivo and in vivo assays. Results show that OvCa cell adhesion to the peritoneum was increased under compression. Moreover, compressive loads stimulated remodeling of peritoneal mesothelial cell surface ultrastructure via induction of tunneling nanotubes (TNT). TNT-mediated interaction between peritoneal mesothelial cells and OvCa cells was enhanced under compression and was accompanied by transport of mitochondria from mesothelial cells to OvCa cells. Additionally, peritoneal collagen fibers adopted a more linear anisotropic alignment under compression, a collagen signature commonly correlated with enhanced invasion in solid tumors. Collectively, these findings elucidate a new role for ascites-induced compression in promoting metastatic OvCa progression.
Identifiants
pubmed: 32681052
doi: 10.1038/s41598-020-68639-2
pii: 10.1038/s41598-020-68639-2
pmc: PMC7367827
doi:
Substances chimiques
Collagen
9007-34-5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
11913Subventions
Organisme : NCI NIH HHS
ID : R01 CA109545
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA214043
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA210210
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA236979
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA168524
Pays : United States
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