TSPAN1 upregulates MMP2 to promote pancreatic cancer cell migration and invasion via PLCγ.

Pancreatic cancer (PC), a malignancy of the digestive system, has one of the highest rates of metastasis and mortality. It is characterized by the detachment, migration, implantation and infiltration of tumor cells to form metastases or recurrent foci. Tetraspanin 1 a novel member of the superfamily, is highly expressed in many types of cancer, including gastric, colon, liver and esophageal cancer. It has also been associated with lymph node metastasis, tumor recurrence and metastasis. However, the role of in PC has not been fully elucidated. The aim of the present study was to determine the expression of Tduanyu1842N1 in human PC tissue samples and cell lines. Additionally, the functions of Tduanyu1842N1 in PC cell migration and invasion were assessed. The protein and gene expression of Tduanyu1842N1 was analyzed in clinical PC tissue samples and human PC cell lines (SW1990, BxPC3, Capan1 and PANC‑1) via immunohistochemistry, reverse transcription‑quantitative polymerase chain reaction and western blotting. The effect of Tduanyu1842N1 downregulation and overexpression in PC cells, via transfection with siRNA and recombinant plasmid, respectively, on cell invasion and migration were assessed. Additionally, the mRNA expression of matrix metalloproteinase (MMP2) and MMP9 were determined. In clinical PC tissue samples, the expression of Tduanyu1842N1 was markedly increased when compared with normal pancreatic tissue samples. Tduanyu1842N1 was also highly expressed in PC cell lines compared with HPDE, a normal pancreatic cell line. Transfection with siRNA targeting Tduanyu1842N1 in PC cell lines significantly suppressed PC cell migration and invasion, and downregulated the expression of MMP2. However, there was no effect on MMP9. Consistently, PC cell migration and invasion together with MMP2 mRNA expression were markedly increased following Tduanyu1842N1 ectopic overexpression. The present study utilized small interfering RNAs (siRNA) targeted to phospholipase Cγ (PLCγ) to demonstrate that Tduanyu1842N1 siRNA suppressed PC cell migration and invasion, and MMP2 mRNA expression by blocking the translocation and phosphorylation of PLCγ. The results of the present study revealed that Tduanyu1842N1 has an important function in human PC cell migration and invasion by modulating MMP2 expression via PLCγ. Thus, the results indicate that the silencing of Tduanyu1842N1 may be a potential therapeutic target for the treatment of PC.

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