51. Involvement of highly sulfated chondroitin sulfate in the metastasis of the Lewis lung carcinoma cells.
- Author
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Li, F., Dam, G.B. ten, Murugan, S., Yamada, S., Hashiguchi, T., Mizumoto, S., Oguri, K., Okayama, M., Kuppevelt, A.H.M.S.M. van, Sugahara, K., Li, F., Dam, G.B. ten, Murugan, S., Yamada, S., Hashiguchi, T., Mizumoto, S., Oguri, K., Okayama, M., Kuppevelt, A.H.M.S.M. van, and Sugahara, K.
- Abstract
Contains fulltext : 69607.pdf (Publisher’s version ) (Open Access), The altered expression of cell surface chondroitin sulfate (CS) and dermatan sulfate (DS) in cancer cells has been demonstrated to play a key role in malignant transformation and tumor metastasis. However, the functional highly sulfated structures in CS/DS chains and their involvement in the process have not been well documented. In the present study, a structural analysis of CS/DS from two mouse Lewis lung carcinoma (3LL)-derived cell lines with different metastatic potentials revealed a higher proportion of Delta(4,5)HexUA-GalNAc(4,6-O-disulfate) generated from E-units (GlcUA-GalNAc(4, 6-O-disulfate)) in highly metastatic LM66-H11 cells than in low metastatic P29 cells, although much less CS/DS is expressed by LM66-H11 than P29 cells. This key finding prompted us to study the role of CS-E-like structures in experimental lung metastasis. The metastasis of LM66-H11 cells to lungs was effectively inhibited by enzymatic removal of tumor cell surface CS or by preadministration of CS-E rich in E-units in a dose-dependent manner. In addition, immunocytochemical analysis showed that LM66-H11 rather than P29 cells expressed more strongly the CS-E epitope, which was specifically recognized by the phage display antibody GD3G7. More importantly, this antibody and a CS-E decasaccharide fraction, the minimal structure recognized by GD3G7, strongly inhibited the metastasis of LM66-H11 cells probably by modifying the proliferative and invading behavior of the metastatic tumor cells. These results suggest that the E-unit-containing epitopes are involved in the metastatic process and a potential target for the diagnosis and treatment of malignant tumors.
- Published
- 2008