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Published on: January 26, 2024
Annexin A7 suppresses lymph node metastasis of hepatocarcinoma cells in a mouse model
Yanling Jin, Shaoqing Wang, Wenjing Chen
1Department of Pathology, Dalian Medical University, 9 West Lvshun Southern Road, Dalian 116044, P,R, China. jwtang_53@sina.cn.
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 FANXA7-control group was 77%, and the lymph node metastasis rate of the FANXA7-down group was 100% (p<0.05). In contrast, the lymph node metastasis rate of the PANXA7-up group was 0% and that of the PANXA7-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.
Insights
Annexin A7 (ANXA7) inhibits hepatocellular carcinoma (HCC) lymph node metastasis. Upregulating ANXA7 prevented metastasis, while its knockdown accelerated it, highlighting ANXA7's role in controlling HCC spread.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Metastasis Research
Background:
- Hepatocellular carcinoma (HCC) is a major cause of cancer mortality in China.
- Investigating novel therapeutic targets for HCC metastasis is crucial.
Purpose of the Study:
- To determine the role of Annexin A7 (ANXA7) in inhibiting HCC lymph node metastasis.
- To evaluate the impact of ANXA7 expression levels on HCC metastasis in a preclinical model.
Main Methods:
- Established HCC mouse models with stable Annexin A7 (ANXA7) knockdown and overexpression.
- Injected modified HCC cells into mouse footpads to induce primary and metastatic tumors.
- Monitored tumor development and performed immunohistochemistry to assess ANXA7 expression and localization.
Main Results:
- Knockdown of ANXA7 significantly increased lymph node metastasis rates (77% control vs. 100% knockdown).
- Overexpression of ANXA7 completely inhibited lymph node metastasis (0% vs. 36% control).
- ANXA7 protein was primarily localized in the cytosol of tumor cells, with altered expression of specific isoforms during progression.
Conclusions:
- Annexin A7 (ANXA7) expression effectively inhibits HCC lymph node metastasis.
- Downregulation of ANXA7 promotes HCC metastasis to regional lymph nodes.
- ANXA7 represents a potential therapeutic target for preventing HCC metastasis.

