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.