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Thrombospondin 2 promotes tumor metastasis by inducing matrix metalloproteinase-13 production in lung cancer cells.

Abstract：

:Thrombospondin (TSP)-2, a matricellular glycoprotein of the TSP family, regulates multiple biological functions, including proliferation, angiogenesis, cell adhesion, and extracellular matrix (ECM) modeling. The clinical relevance of TSP-2 has been explored in many different cancers. TSP-2 expression levels vary between different cancer types, and their role in tumor progression remains controversial. Although previous studies have reported higher serum TSP-2 levels in patients with non-small cell lung cancer, the role of TSP-2 in lung cancer progression remains to be addressed. A total of 585 lung adenocarcinoma datasets, including mRNA sequencing and clinical data, were retrieved from The Cancer Genome Atlas (TCGA). Forty paired adjacent normal tissues and lung tumor tissue datasets were used to examine TSP-2 expression levels. Tumor microarray were performed with immunohistochemical staining to examine TSP-2 expression in lung cancer patients. Transwell migration assay, quantitative real-time PCR and Western blot were used to investigate molecular mechanism of TSP-2 in lung cancer cell. TSP-2 promotes matrix metalloproteinase-13 (MMP-13) expression, cell migration, and cell invasion by mediating integrin αvβ3/FAK/Akt/NF-κB signal transduction. Using TSP-2 knockdown stable cell lines, we found that TSP-2 knockdown reduces MMP-13 expression and cell mobility. When we manipulated the tumor tissue microarray and TCGA datasets to investigate the clinical relevance of TSP-2, we found high TSP-2 expression levels in lung cancer specimens. The present study demonstrates that TSP-2 regulates cell mobility through MMP-13 expression in lung cancer cells. In addition, TSP-2 expression was associated with MMP-13 expression and poor prognosis in lung cancer. TSP-2 may therefore be a promising novel target for lung cancer treatment.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Liu JF,Lee CW,Tsai MH,Tang CH,Chen PC,Lin LW,Lin CY,Lu CH,Lin YF,Yang SH,Chao CC

doi

10.1016/j.bcp.2018.07.024

subject

Has Abstract

pub_date

2018-09-01 00:00:00

pages

537-546

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(18)30292-2

journal_volume

155

pub_type

杂志文章

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Thrombospondin 2 promotes tumor metastasis by inducing matrix metalloproteinase-13 production in lung cancer cells.