INHIBITION OF TUMOR-CELL HAPTOTAXIS BY SODIUM D-GLUCARO-DELTA-LACTAM (ND2001)

We used the Boyden chamber system to investigate the mechanism by whic h the antimetastatic agent sodium n-glucaro-delta-lactam (ND2001) inhi bits tumor cell invasion, and by establishing what ND2001 did not achi eve, we were able to pinpoint the areas in which it was successful as an inhibitor, ND2001 did not inhibit cell adhesion of a highly metasta tic B16 melanoma variant (the B16 variant) to the reconstituted basal membrane Matrigel, nor did it affect the production or activity of bas al membrane-degrading type IV collagenase, but, in the Boyden chamber, ND2001 inhibited cell migration of the B16 variant toward a chemoattr actant, laminin, on the lower surface of a Matrigel-free filter set (h aptotaxis). Lewis lung carcinoma (3LL) cells that had been treated wit h ND2001 also exhibited hardly any haptotaxis, although the cells show ed no alteration in behavior during cell adhesion to Matrigel. Since N D2001 did succeed in inhibiting the pulmonary metastases of the B16 va riant and 3LL, we infer that inhibition of the metastases by ND2001 in these tumors is likely to be due to the inhibition of haptotactic mig ration.