{Reference Type}: Journal Article
{Title}: Matrix metalloproteinase-11 regulates inverted papilloma epithelial cell migration and invasion.
{Author}: Panara K;Hui TL;Keshari D;Tong CCL;Palmer JN;Adappa ND;Douglas JE;Cohen NA;Kohanski MA;
{Journal}: Int Forum Allergy Rhinol
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jul 5
{Factor}: 5.426
{DOI}: 10.1002/alr.23405
{Abstract}: <B>BACKGROUND: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.