Fluid-sensitive migration mechanisms predict association between metastasis and high interstitial fluid pressure in pancreatic cancer.

Autor: Nævdal G; NORCE Norwegian Research Centre AS, Bergen, Norway., Rofstad EK; Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., Søreide K; Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway; Department of Clinical Medicine, University of Bergen, Norway; Gastrointestinal Translational Research Group, Laboratory for Molecular medicine, Stavanger University Hospital, Norway., Evje S; Faculty of Science and Technology, Group of Computational Engineering, University of Stavanger, Norway. Electronic address: steinar.evje@uis.no.
Jazyk: angličtina
Zdroj: Journal of biomechanics [J Biomech] 2022 Dec; Vol. 145, pp. 111362. Date of Electronic Publication: 2022 Oct 29.
DOI: 10.1016/j.jbiomech.2022.111362
Abstrakt: A remarkable feature in pancreatic cancer is the propensity to metastasize early, even for small, early stage cancers. We use a computer-based pancreatic model to simulate tumor progression behavior where fluid-sensitive migration mechanisms are accounted for as a plausible driver for metastasis. The model has been trained to comply with in vitro results to determine input parameters that characterize the migration mechanisms. To mimic previously studied preclinical xenografts we run the computer model informed with an ensemble of stochastic-generated realizations of unknown parameters related to tumor microenvironment only constrained such that pathological realistic values for interstitial fluid pressure (IFP) are obtained. The in silico model suggests the occurrence of a steady production of small clusters of cancer cells that detach from the primary tumor and form isolated islands and thereby creates a natural prerequisite for a strong invasion into the lymph nodes and venous system. The model predicts that this behavior is associated with high interstitial fluid pressure (IFP), consistent with published experimental findings. The continuum-based model is the first to explain published results for preclinical models which have reported associations between high IFP and high metastatic propensity and thereby serves to shed light on possible mechanisms behind the clinical aggressiveness of pancreatic cancer.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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