A metastatic tumor cell line has greatly reduced levels of a specific homotypic cell adhesion molecule activity.

The first step in tumor metastasis is the detachment of cells from the primary tumor. If metastatic tumor cells have decreased levels of active homotypic cell adhesion molecules (CAMs), this might aid their escape from the primary tumor. In order to determine whether homotypic CAM activity might be reduced in metastatic cells, a new direct CAM assay was developed. The assay gave a linear response with respect to the concentration of a CAM fragment preparation from Balb/3T3 cells and was able to follow partial purifications of the CAM activity. The yield of homotypic CAM activity was measured from metastatic cells, related tumorigenic but nonmetastatic cells, and parental cells. The parental Balb/3T3 and nonmetastatic Balb/3T3 MSV85 cells yielded 22.5 +/- 1.1 (SD) and 24.8 +/- 3.5 units of CAM activity per mg of protein, whereas the metastatic Balb/3T3 K234 cells yielded only 4.6 +/- 0.8 units/mg. The homotypic adhesiveness of each of the cell lines was closely correlated with the level of CAM activity. When the CAM activity from each of the three cell lines was serially fractionated with the same column, the parental Balb/3T3 and nonmetastatic Balb/3T3 MSV85 cells each had one major peak of CAM activity that eluted in the same place. However, the metastatic Balb/3T3 K234 cells were missing this peak of CAM activity. These results suggest that levels of homotypic CAM activity are greatly reduced in a metastatic cell line because the cells are missing a specific CAM activity. This would presumably allow the metastatic cells to escape more easily from the primary tumor and provide a molecular explanation for how they can complete the first step in metastasis.