Hyaluronan on the surface of tumor cells is correlated with metastatic behavior.

In the present study, we examined the metastatic potential of tumor cells expressing different levels of cell surface hyaluronan. We used flow cytometry to isolate subsets of the B16-F1 mouse melanoma cell line that expressed either high (HA-H) or low (HA-L) amounts of hyaluronan on their surfaces. These two subsets of cells showed a 32-fold difference in the amount of cell surface hyaluronan, due to its rate of synthesis. However, these cell lines did not differ from each other with regard to their in vitro growth rates, susceptibility to natural killer-mediated cytotoxicity, or the expression of the cell surface proteins CD44, ICAM-1, and GMP-140. When these cells were injected s.c., they both formed s.c. tumors of approximately the same size. However, when injected into the tail vein of mice, the HA-H cells formed a greater number of nodules in the lungs and caused a faster rate of mortality than the HA-L cells. The presence of hyaluronan did enhance the interaction of the HA-H cells with cultured endothelial cells that expressed CD44. Thus, it is possible that enhanced interactions between hyaluronan and CD44 promoted the formation of tumor embolisms which, in turn, increased the chances that the tumor cells would be trapped in the lungs. Taken together, these results suggest that hyaluronan may play a critical role in the process of tumor metastasis.