Annexin A7 suppresses lymph node metastasis of hepatocarcinoma cells in a mouse model

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death in China. This study investigated the effects of Annexin A7 (ANXA7) on the inhibition of HCC lymph node metastasis in a mouse model. METHODS: The stable knockup and knockdown of Annexin A7-expressing HCC cells using Annexin A7 cDNA and shRNA vectors, respectively, were injected into a mouse footpad to establish primary and metastatic tumors in mice. On the 14th, 21st, and 28th days after HCC cells inoculation, the mice were sacrificed for inspection of primary and secondary tumors and immunohistochemistry of Annexin A7 expression. RESULTS: The lymph node metastasis rate of the F(ANXA7-control) group was 77%, and the lymph node metastasis rate of the F(ANXA7-down) group was 100% (p < 0.05). In contrast, the lymph node metastasis rate of the P(ANXA7-up) group was 0% and that of the P(ANXA7-control) group was 36% (p < 0.05). Furthermore, immunohistochemistry experiments revealed that the subcellular localization of Annexin A7 protein in both primary and lymph node-metastasized tumors was mainly in the cytosol. In addition, the expression of the 47 kDa and 51 kDa isoforms of Annexin A7 protein changed during tumor progression. CONCLUSION: This study indicated that Annexin A7 expression was able to inhibit HCC lymph node metastasis, whereas knockdown of Annexin A7 expression significantly induced HCC metastasis to local lymph nodes.