Matrix metalloproteinase-11 regulates inverted papilloma epithelial cell migration and invasion.

epithelial migration inverted papilloma matrix metalloproteinase‐11

Journal

International forum of allergy & rhinology
ISSN: 2042-6984
Titre abrégé: Int Forum Allergy Rhinol
Pays: United States
ID NLM: 101550261

Informations de publication

Date de publication:
05 Jul 2024
Historique:
revised: 17 06 2024
received: 29 03 2024
accepted: 24 06 2024
medline: 5 7 2024
pubmed: 5 7 2024
entrez: 5 7 2024
Statut: aheadofprint

Résumé

Inverted papilloma (IP) is a benign tumor characterized by epithelial proliferation, which has the potential for malignant transformation. However, the mechanisms driving this transformation are poorly defined. Matrix metalloproteinase-11 (MMP-11), a regulator of the tumor microenvironment that degrades extracellular matrix, is upregulated in IP with dysplasia. Here, we aim to investigate the role of MMP-11 in IP epithelial migration and invasion. Human IP and contralateral normal sinus mucosa (control) samples were obtained. IP-derived epithelial cultures and normal mucosa-derived epithelial cultures were grown in air‒liquid interface, followed by immunostaining to assess MMP-11 expression in IP. Migration and invasion assays were used to evaluate the role of an anti-MMP-11 antibody on IP and control epithelial cultures. IP-derived cultures demonstrated strong MMP-11 expression compared to controls. Treatment with anti-MMP-11 blocking antibody significantly reduced epithelial migration only in IP-derived cells compared to non-treated IP cells, as seen by incomplete wound closure and reduced transepithelial resistance. In addition, inhibition of MMP-11 reduced IP epithelia's ability to invade through collagen-coated transwells, suggesting that MMP-11 plays a role in invasion. We established an in vitro model to study IP-derived epithelial cells. MMP-11 is uniquely expressed in IP epithelial cultures compared to control epithelial cultures. Inhibition of MMP-11 limits IP epithelial migration and invasion to levels similar to that of normal sinus mucosa. MMP-11 does not appear to have a functional role in normal sinus epithelium, suggesting that MMP-11 has a role in malignant transformation of IP.

Sections du résumé

BACKGROUND BACKGROUND
Inverted papilloma (IP) is a benign tumor characterized by epithelial proliferation, which has the potential for malignant transformation. However, the mechanisms driving this transformation are poorly defined. Matrix metalloproteinase-11 (MMP-11), a regulator of the tumor microenvironment that degrades extracellular matrix, is upregulated in IP with dysplasia. Here, we aim to investigate the role of MMP-11 in IP epithelial migration and invasion.
METHODS METHODS
Human IP and contralateral normal sinus mucosa (control) samples were obtained. IP-derived epithelial cultures and normal mucosa-derived epithelial cultures were grown in air‒liquid interface, followed by immunostaining to assess MMP-11 expression in IP. Migration and invasion assays were used to evaluate the role of an anti-MMP-11 antibody on IP and control epithelial cultures.
RESULTS RESULTS
IP-derived cultures demonstrated strong MMP-11 expression compared to controls. Treatment with anti-MMP-11 blocking antibody significantly reduced epithelial migration only in IP-derived cells compared to non-treated IP cells, as seen by incomplete wound closure and reduced transepithelial resistance. In addition, inhibition of MMP-11 reduced IP epithelia's ability to invade through collagen-coated transwells, suggesting that MMP-11 plays a role in invasion.
CONCLUSION CONCLUSIONS
We established an in vitro model to study IP-derived epithelial cells. MMP-11 is uniquely expressed in IP epithelial cultures compared to control epithelial cultures. Inhibition of MMP-11 limits IP epithelial migration and invasion to levels similar to that of normal sinus mucosa. MMP-11 does not appear to have a functional role in normal sinus epithelium, suggesting that MMP-11 has a role in malignant transformation of IP.

Identifiants

pubmed: 38967558
doi: 10.1002/alr.23405
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : ARS Resident Research
Organisme : American Rhinologic Society
ID : Resident Core Grant #1060942

Informations de copyright

© 2024 The Author(s). International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.

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Auteurs

Kush Panara (K)

Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Tan Li Hui (TL)

Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Deepa Keshari (D)

Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Charles C L Tong (CCL)

Department of Otolaryngology-Head and Neck Surgery, Lenox Hill Hospital/Long Island Jewish Hospital, Northwell, New Hyde Park, New York, New York, USA.
Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA.

James N Palmer (JN)

Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Nithin D Adappa (ND)

Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Jennifer E Douglas (JE)

Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Monell Chemical Senses Institute, Philadelphia, Pennsylvania, USA.

Noam A Cohen (NA)

Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Monell Chemical Senses Institute, Philadelphia, Pennsylvania, USA.
Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA.

Michael A Kohanski (MA)

Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Classifications MeSH