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

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.

Autophagy Modulates the Migration of Retinal Pericytes Induced by Advanced Glycation End Products

“…MMP-2 is one of the most widely distributed subtypes of the MMPs family. MMP-2 has been found in retinal pericytes, which plays an important role in promoting various cellular migrations as well [ 32 – 34 ]. Following the treatment with AGE-BSA, current data showed decreased expression of vinculin and increased expression of MMP-2, further confirming they both participate in promoting cell migration.…”

Periostin in ovarian carcinoma: from heterogeneity to prognostic value

“…Solid evidence shows that periostin (POSTN) could be one of these novel biomarkers. The focus on POSTN is partially based on its role in the communication between tumor cells and extracellular matrix (ECM), contributing to tumor progression and metastasis in various types of cancers [12][13][14][15][16][17][18][19][20][21][22][23].…”

“…Several reports have been focused on POSTN expression in different types of neoplasia, since the 2000's, such as lung [19,20], breast [36], prostate [22], colon [23], head and neck [37], pancreatic [38], and esophageal carcinomas [18]. POSTN serum and tissue overexpression is correlated with unfavorable outcomes in non-small cell lung cancer [19,20,39] and poor prognosis in ovarian [12,40,41] and breast [36] cancer.…”

The Role of Periostin in Angiogenesis and Lymphangiogenesis in Tumors

“…The FAS1 domain acts as a ligand of integrins of the cell membrane. In turn, the C-terminal region consists of a hydrophilic domain that regulates ECM organization and allows for interactions by binding ECM proteins such as type I and V collagen, fibronectin and glycosaminoglycans [ 43 , 44 , 48 , 49 ].…”