Original Research
Copyright ©The Author(s) 2001. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 15, 2001; 7(4): 532-536
Published online Aug 15, 2001. doi: 10.3748/wjg.v7.i4.532
Molecular mechanism about lymphogenous metastasis of hepatocarcinoma cells in mice
Li Hou, Ying Li, Yong-Hua Jia, Bo Wang, Yi Xin, Mao-Ying Ling, Shen Lü
Li Hou, Ying Li, Yong-Hua Jia, Bo Wang, Mao-Ying Ling, Shen Lü, Department of Pathology, Dalian Medical University, Dalian 116027, Liaoning Province, China
Yi Xin, Department of Biochemistry, Dalian Medical University, Dalian 116027, Liaoning Province, China
Author contributions: All authors contributed equally to the work.
Supported by the National Natural Science Foundation of China, No. 39470776
Correspondence to: Shen Lü MD., PhD. Department of Pathology, Dalian Medical University, Dalian 116027, China. Houli72@163.net
Telephone: 0086-411-4720226
Received: February 6, 2001
Revised: February 8, 2001
Accepted: February 12, 2001
Published online: August 15, 2001
Abstract

AIM: To investigate the correlation between lymphogenous metastasis and matrix metalloproteinases (MMPs) activity and the expression of Fas ligand of tumor cells in lymph nodes.

METHODS: Fifty-six inbred 615-mice were equally divided into 2 groups and inoculated with Hca-F and Hca-P cells. Their lymph node metastatic rates were examined. Growth fraction of lymphocytes in host lymph nodes was detected by flow cytometry. The Hca-F and Hca-P cells were cultured with extract of lymph node, liver or spleen. The quantity of MMPs in these supernatants was examined by zymographic analysis. The expression of Fas ligand, PCNA, Bcl-2 protein of Hca-F and Hca-P cells in the mice were examined by immunohistochemistry. The apoptosis signals of macrophages in lymph nodes were observed with in situ DNA fragmentation.

RESULTS: On the 28th day post-inoculation, the lymph node metastatic rate of Hca-F was 80% (16/20), whereas that of Hca-P was 25% (5/20). The growth fraction of lymphocytes was as follows: in the Hca-F cells, the proliferating peak of lymphocytes appeared on the 14th day post-inoculation and then decreased rapidly, while in Hca-P cells, the peak appeared on the 7th day post inoculation and then kept at a high level. With the extract of lymph node, the quantity of the MMP-9 activity increased (P < 0.01) and active MMP-9 and MMP-2 were produced by both Hca-F and Hca-P tumor cells, which did not produce MMPs without the extract of lymph node or with the extracts of the liver and spleen. The expression of Fas Ligand of Hca-F cells was stronger than that of Hca-P cells (P < 0.01). The expressions of PCNA and Bcl-2 protein of Hca-F cells in the tumors of inoculated area were the same as that of Hca-P cells. In situ DNA fragmentation showed that the positive signals of macrophages were around Hca-F cells.

CONCLUSION: Secretion of MMPs which was associated with metastatic ability of Hca-F and Hca-P tumor cells depends on the environment of lymph nodes. The increased expression of Fas ligand protein of Hca-F tumor cells with high lymphogenous metastatic potential in lymph nodes may help tumor cells escape from being killed by host lymphocytes.

Keywords: liver neoplasms/pathology; lymphatic metastasis; tumor cells, cultured; metalloproteinases/secretion