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

IF 7.2 2区医学 Q1 OTORHINOLARYNGOLOGY International Forum of Allergy & Rhinology Pub Date : 2024-07-05 DOI:10.1002/alr.23405

Kush Panara MD, Tan Li Hui PhD, Deepa Keshari PhD, Charles C. L. Tong MD, James N. Palmer MD, Nithin D. Adappa MD, Jennifer E. Douglas MD, Noam A. Cohen MD, PhD, Michael A. Kohanski MD, PhD

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Abstract

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

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

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

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.

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基质金属蛋白酶-11调节倒置乳头状瘤上皮细胞的迁移和侵袭。

背景：倒置乳头状瘤（IP）是一种以上皮增生为特征的良性肿瘤，有恶变的可能。然而，这种转化的驱动机制尚不明确。基质金属蛋白酶-11（MMP-11）是一种降解细胞外基质的肿瘤微环境调节剂，在发育不良的 IP 中上调。在此，我们旨在研究 MMP-11 在 IP 上皮迁移和侵袭中的作用。方法：获取人类 IP 和对侧正常鼻窦粘膜（对照）样本，在气液界面中培养 IP 衍生上皮细胞和正常粘膜衍生上皮细胞，然后用免疫染色法评估 IP 中 MMP-11 的表达。迁移和侵袭试验用于评估抗 MMP-11 抗体对 IP 和对照上皮细胞培养物的作用：结果：与对照组相比，IP衍生培养物显示出较强的MMP-11表达。与未处理的 IP 细胞相比，用抗 MMP-11 阻断抗体处理只能显著降低 IP 衍生细胞的上皮迁移，表现为伤口闭合不全和跨上皮阻力降低。此外，抑制 MMP-11 还能降低 IP 上皮细胞通过胶原包被的透孔侵入的能力，这表明 MMP-11 在侵入中发挥作用：我们建立了一个体外模型来研究 IP 衍生上皮细胞。与对照上皮细胞培养物相比，MMP-11在IP上皮细胞培养物中有独特的表达。抑制 MMP-11 可将 IP 上皮细胞的迁移和侵袭限制在与正常鼻窦粘膜相似的水平。MMP-11在正常鼻窦上皮中似乎没有功能性作用，这表明MMP-11在IP的恶性转化中发挥作用。

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来源期刊

International Forum of Allergy & Rhinology OTORHINOLARYNGOLOGY-

CiteScore

11.70

自引率

10.90%

发文量

185

审稿时长

6-12 weeks

期刊介绍： International Forum of Allergy & Rhinologyis a peer-reviewed scientific journal, and the Official Journal of the American Rhinologic Society and the American Academy of Otolaryngic Allergy. International Forum of Allergy Rhinology provides a forum for clinical researchers, basic scientists, clinicians, and others to publish original research and explore controversies in the medical and surgical treatment of patients with otolaryngic allergy, rhinologic, and skull base conditions. The application of current research to the management of otolaryngic allergy, rhinologic, and skull base diseases and the need for further investigation will be highlighted.