Platelet and epithelial cell interations can be modeled in cell culture, and are not affected by dihomo-gamma-linolenic acid.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2024
Historique:
received: 10 01 2024
accepted: 06 08 2024
medline: 27 8 2024
pubmed: 27 8 2024
entrez: 27 8 2024
Statut: epublish

Résumé

Increasing evidence is implicating roles for platelets in the development and progression of ovarian cancer, a highly lethal disease that can arise from the fallopian tubes, and has no current method of early detection or prevention. Thrombosis is a major cause of mortality of ovarian cancer patients suggesting that the cancer alters platelet behavior. The objective of this study was to develop a cell culture model of the pathological interactions of human platelets and ovarian cancer cells, using normal FT epithelial cells as a healthy control, and to test effects of the anti-platelet dihomo-gamma-linolenic acid (DGLA) in the model. Both healthy and cancer cells caused platelet aggregation, however platelets only affected spheroid formation by cancer cells and had no effect on healthy cell spheroid formation. When naturally-formed spheroids of epithelial cells were exposed to platelets in transwell inserts that did not allow direct interactions of the two cell types, platelets caused increased size of the spheroids formed by cancer cells, but not healthy cells. When cancer cell spheroids formed using magnetic nanoshuttle technology were put in direct physical contact with platelets, the platelets caused spheroid condensation. In ovarian cancer cells, DGLA promoted epithelial-to-mesenchymal (EMT) transition at doses as low as 100 μM, and inhibited metabolic viability and induced apoptosis at doses ≥150 μM. DGLA doses ≤150 μM used to avoid direct DGLA effects on cancer cells, had no effect on the pathological interactions of platelets and ovarian cancer cells in our models. These results demonstrate that the pathological interactions of platelets with ovarian cancer cells can be modeled in cell culture, and that DGLA has no effect on these interactions, suggesting that targeting platelets is a rational approach for reducing cancer aggressiveness and thrombosis risk in ovarian cancer patients, however DGLA is not an appropriate candidate for this strategy.

Identifiants

pubmed: 39190751
doi: 10.1371/journal.pone.0309125
pii: PONE-D-23-43388
doi:

Substances chimiques

8,11,14-Eicosatrienoic Acid FC398RK06S

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0309125

Informations de copyright

Copyright: © 2024 Isingizwe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

Auteurs

Zitha Redempta Isingizwe (ZR)

Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America.

Laura F Mortan (LF)

Department of Pathology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America.

Doris Mangiaracina Benbrook (DM)

Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America.
Department of Pathology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America.

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Classifications MeSH