In:
PLOS Computational Biology, Public Library of Science (PLoS), Vol. 18, No. 10 ( 2022-10-24), p. e1010153-
Abstract:
Early lung cancer lesions develop within a unique microenvironment that undergoes constant cyclic stretch from respiration. While tumor stiffening is an established driver of tumor progression, the contribution of stress and strain to lung cancer is unknown. We developed tissue scale finite element models of lung tissue to test how early lesions alter respiration-induced strain. We found that an early tumor, represented as alveolar filling, amplified the strain experienced in the adjacent alveolar walls. Tumor stiffening further increased the amplitude of the strain in the adjacent alveolar walls and extended the strain amplification deeper into the normal lung. In contrast, the strain experienced in the tumor proper was less than the applied strain, although regions of amplification appeared at the tumor edge. Measurements of the alveolar wall thickness in clinical and mouse model samples of lung adenocarcinoma (LUAD) showed wall thickening adjacent to the tumors, consistent with cellular response to strain. Modeling alveolar wall thickening by encircling the tumor with thickened walls moved the strain amplification radially outward, to the next adjacent alveolus. Simulating iterative thickening in response to amplified strain produced tracks of thickened walls. We observed such tracks in early-stage clinical samples. The tracks were populated with invading tumor cells, suggesting that strain amplification in very early lung lesions could guide pro-invasive remodeling of the tumor microenvironment. The simulation results and tumor measurements suggest that cells at the edge of a lung tumor and in surrounding alveolar walls experience increased strain during respiration that could promote tumor progression.
Type of Medium:
Online Resource
ISSN:
1553-7358
DOI:
10.1371/journal.pcbi.1010153
DOI:
10.1371/journal.pcbi.1010153.g001
DOI:
10.1371/journal.pcbi.1010153.g002
DOI:
10.1371/journal.pcbi.1010153.g003
DOI:
10.1371/journal.pcbi.1010153.g004
DOI:
10.1371/journal.pcbi.1010153.g005
DOI:
10.1371/journal.pcbi.1010153.g006
DOI:
10.1371/journal.pcbi.1010153.t001
DOI:
10.1371/journal.pcbi.1010153.t002
DOI:
10.1371/journal.pcbi.1010153.s001
DOI:
10.1371/journal.pcbi.1010153.s002
DOI:
10.1371/journal.pcbi.1010153.s003
DOI:
10.1371/journal.pcbi.1010153.s004
DOI:
10.1371/journal.pcbi.1010153.s005
DOI:
10.1371/journal.pcbi.1010153.s006
DOI:
10.1371/journal.pcbi.1010153.r001
DOI:
10.1371/journal.pcbi.1010153.r002
DOI:
10.1371/journal.pcbi.1010153.r003
DOI:
10.1371/journal.pcbi.1010153.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2193340-6
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