Skip to main content

ORIGINAL RESEARCH article

Front. Oncol.
Sec. Molecular and Cellular Oncology
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1456346

Extracellular vesicles from cancer cell lines of different origins drive the phenotype of normal oral fibroblasts in a CAF-like direction

Provisionally accepted
Tine M Søland Tine M Søland Aleksandra Lipka Aleksandra Lipka Ann-Kristin Ruus Ann-Kristin Ruus Ann-Kristin Molværsmyr Ann-Kristin Molværsmyr Hilde Kanli Galtung Hilde Kanli Galtung *Trude M. Haug Trude M. Haug
  • Institute of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway

The final, formatted version of the article will be published soon.

    Normal oral fibroblasts (NOFs) are located in the connective tissue of the oral mucosa. The NOFs play an important role in wound healing, tumor progression, and metastasis. They are subjected to influence by external and internal stimuli, among them extracellular vesicles (EVs), that are considered as important players in cell to cell communication, especially in carcinogenesis and metastatic processes. During tumorigenesis, stromal NOFs may undergo activation into cancerassociated fibroblasts (CAFs) that modify their phenotype to provide pro-oncogenic signals that in turn facilitate tumor initiation, progression, and metastasis. The aim of the study was to reveal the effect of EVs derived from local (oral squamous cell carcinoma -OSCC) and distant (pancreatic adenocarcinoma -PDAC; malignant melanoma brain metastasis -MBM) cancer origin on NOFs and their possible change into a CAF-like direction. The effect of each of the cancer EV types on NOFs proliferation, viability, and migration was tested. Also, changes in gene expression of the wellestablished CAF biomarkers ACTA2, FAP, PDGFR, and two putative CAF biomarkers, the Ca2+activated ion channels ANO1 and KCNMA, were studied. Obtained results indicate that NOFs receive and process signals transmitted by EVs originating from both OSCC, PDAC, and MBM. The fibroblast response was dependent on EV origin and concentration, and duration of EV exposure. The present results indicate that the molecular cargo of the EVs direct NOFs towards a pro-tumorigenic phenotype.

    Keywords: oral cancer, oral squamous cell carcinoma, cancer-associated fibroblasts, phenotype, proliferation, Migration, EV, OSCC

    Received: 03 Jul 2024; Accepted: 06 Sep 2024.

    Copyright: © 2024 Søland, Lipka, Ruus, Molværsmyr, Kanli Galtung and Haug. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Hilde Kanli Galtung, Institute of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.