Heparanase regulates in vitro VEGF-C expression and its clinical significance to pancreatic ductal cell adenocarcinoma

Author:        

Publisher: Spandidos Publications

E-ISSN: 1792-1082|11|2|1327-1334

ISSN: 1792-1074

Source: Oncology Letters, Vol.11, Iss.2, 2016-01, pp. : 1327-1334

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Abstract

Heparanase (HPSE) and vascular endothelial growth factor C (VEGF-C) are important cytokines that promote metastasis and angiogenesis in numerous malignant neoplasms, however, their association remains unclear in pancreatic ductal cell adenocarcinoma (PDAC). The present study aimed to investigate whether HPSE has a positive correlation with VEGFC expression and to uncover the role it plays in the in vitro invasion of BxPC3 cells (a pancreatic carcinoma cell line), and to analyze the value of joint detection of HPSE and VEGFC for PDAC patients. A recombinant plasmid, GV230/HPSE was constructed and BxPC3 cells were transiently transfected with GV230/HPSE or siRNA against HPSE. The expression levels of HPSE and VEGFC were compared using reverse transcription quantitative PCR (RTqPCR) and immunoblotting. The metastatic potential of treated BxPC3 cells was evaluated using a Transwell® invasion assay. The relative mRNA levels of HPSE and VEGFC in 34 PDAC specimens were assessed by RTqPCR. The results of the RTqPCR demonstrated a 10.7 and 3.24fold elevation (P<0.01) of HPSE mRNA and VEGFC mRNA, respectively, in GV230/HPSE group, whereas the HPSE siRNA group were downregulated for these mRNAs (2.45fold, P<0.01; 1.84fold, P<0.01). The same pattern for protein expression was detected using immunoblot assays. In Transwell® invasion assays 138±5 cells in GV230 /HPSE group and 53±4 cells in siRNA group migrated through the Matrigel®. A negative correlation between the mRNA levels of HPSE and VEGFC in PDAC specimens and the prognosis factors of the postoperative patients was identified. Spearman rank correlation analysis indicated a positive correlation between HPSE and VEGFC in PDAC (r=0.812, P<0.01). HPSE regulates the expression of VEGFC and facilitates invasion of BxPC3 in vitro. Joint detection of HPSE and VEGFC may therefore be clinically useful in determining the prognosis of pancreatic cancer patients.

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