Role of Periostin Expression in Non-Small Cell Lung Cancer: Periostin Silencing Inhibits the Migration and Invasion of Lung Cancer Cells via Regulation of MMP-2 Expression.

Katarzyna Ratajczak-Wielgomas,Piotr Dziegiel,Alicja Kmiecik

doi:10.3390/ijms23031240

Katarzyna Ratajczak-Wielgomas, Piotr Dziegiel + Show 1 more

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https://doi.org/10.3390/ijms23031240

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Abstract

The involvement of periostin (POSTN) in non-small-cell lung cancer (NSCLC) migration, invasion, and its underlying mechanisms has not been well established. The present study aims to determine epithelial POSTN expression in NSCLC and to assess associations with clinicopathological factors and prognosis as well as to explore the effects of POSTN knockdown on tumor microenvironment and the migration and invasion of lung cancer cells. Immunohistochemistry was used to evaluate epithelial POSTN expression in NSCLC. POSTN mRNA expression in the dissected lung cancer cells was confirmed by laser capture microdissection and real-time PCR. A549 cells were used for transfecting shRNA-POSTN lentiviral particles. Wound healing and Transwell invasion assays were used to assess the migratory and invasive abilities of A549 cells transfected with POSTN-specific short hairpin (sh)RNA. The results demonstrated significantly higher cytoplasmic POSTN expression in the whole NSCLC group compared to non-malignant lung tissue (NMLT). POSTN expression in cancer cells may be considered to be an independent prognostic factor for survival in NSCLC. POSTN knockdown significantly inhibited A549 cell migration and invasion capabilities in vitro. The activity and the expression level of matrix metalloproteinase-2 (MMP-2) were significantly decreased in A549.shRNA compared to control cells. In summary, POSTN may regulate lung cancer cell invasiveness by modulating the expression of MMP-2 and may represent a potential target for novel therapeutic intervention for NSCLC.

Highlights

Lung cancer, i.e., bronchogenic malignant neoplasms arising from airway epithelioma, is one of the most common malignancies, and 5-year survival rates range from 4% to17%, depending on the stage of the disease at diagnosis [1,2]
Similar conclusions were drawn by Ouanouki et al [50], who indicated that silencing of POSTN inhibited U-87 glioblastoma cell migration and invasive potential, which is in line with the tendency demonstrated in our study
It was found that recombinant POSTN enhanced matrix metalloproteinase -2 (MMP-2) expression in a concentration-dependant manner, which confirms the results obtained earlier on A549 lung cancer cells transfected with

Summary

Introduction

I.e., bronchogenic malignant neoplasms arising from airway epithelioma, is one of the most common malignancies, and 5-year survival rates range from 4% to17%, depending on the stage of the disease at diagnosis [1,2]. Improvements in the knowledge of molecular alterations and their functional significance have the prospective to influence lung cancer diagnosis, prognostication, and treatment [5]. Tumor invasion and metastasis are one of the major causes of lung cancer-associated mortality. The molecular mechanisms underlying cancer cell invasion and migration are complex. The initial events are related to the proteolytic degradation of the extracellular matrix (ECM), which provides biochemical and mechanical barriers to cancer cell migration [7]. ECM degradation requires the expression and activity of matrix metalloproteinases (MMPs), which are known to play a major role in lung cancer by favoring the invasion of cancer cells [7,8]. The inhibition of the MMP-2 expression regulatory pathway is an important therapeutic strategy for preventing lung cancer metastasis

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Conclusion