Background
Tissue factor pathway inhibitor 2 (TFPI‐2) has been recently identified as a tumor suppressor gene in several human cancers, whereas its role in thyroid cancer has been unclear.
Methods
The TFPI‐2 protein level in thyroid cancer tissues and cell lines (8305C and B‐CPAP) were examined using immunohistochemistry and immunoblotting. The TFPI‐2 promoter methylation was examined using methylation‐specific polymerase chain reaction (MSP). Lentivirus containing TFPI‐2 cDNA (Lenti‐TFPI‐2) was constructed to elevate TFPI‐2 expression in 8305C and B‐CPAP cells. The effects of Lenti‐TFPI‐2 on cell proliferation in vitro and in vivo were evaluated by MTT assay and mouse xenograft model. Annexin V/PI double staining assay was performed to detect the effect of Lenti‐TFPI‐2 on cell apoptosis.
Results
TFPI‐2 protein level were decreased in cancer tissues and lymph node metastasis, and TFPI‐2 protein level is positively associated with survival time. The promoter of TFPI‐2 is hypermethylated in cancer tissues. TFPI‐2 mRNA and protein levels were abundant in normal human thyroid follicular cell line Nthy‐ori 3‐1 cells, whereas they were decreased in 8305C and B‐CPAP cells. pcDNA‐TFPI‐2 elevated TFPI‐2 mRNA and protein in 8305C and B‐CPAP cells. TFPI‐2 overexpression suppressed proliferation and induced apoptosis of 8305C and B‐CPAP cells.
Conclusions
TFPI‐2 inactivation may play a role in thyroid cancer tumorigenesis and development. TFPI‐2 overexpression suppressed cell proliferation through induction of cell apoptosis, suggesting that TFPI‐2 may serve as a novel and effective target for thyroid cancer therapy.