LAMININ SURFACE BINDING-SITES AND METASTATIC POTENTIAL OF 3LL TUMOR-CELLS, INCREASED BY INDOMETHACIN

The level of laminin receptor expression on tumor cell surface has been correlated with the capacity of tumor cells to metastasize. In the present work we show that indomethacin treatment of a low metastatic 3LL tumor cells increases the ability of these cells to form lung metastasis and the binding of [125I] laminin on their cell surface. Scatchard analysis showed that the incubation with indomethacin (10-7 M) for 48 h induced a specific increase of laminin binding sites on 3LL cell surface (1.5 fold per cell), presenting both a high and low affinity class of binding sites. On the other hand, indomethacin treatment (2 mg/kg weight) of tumor bearing mice increased the number of spontaneous metastatic nodules on the lung surface. Likewise, when 3LL tumor cells were incubated with indomethacin (10-7 M) for 48 h, we observed an enhancement of lung metastatic nodules after intravenous injection of tumor cells. This last effect was partially reversed by peptides DPGYIGSR or YIGSR, corresponding to the active site at the B1 chain of laminin, with ability to bind the 67-kD laminin cell surface receptors. In summary, our results show that the increased attachment of 3LL tumor cells to laminin mediated by indomethacin is directly correlated with the metastatic activity of these cells, and suggests that the indomethacin effect on the metastatic potential could involve a modulation of laminin receptors on tumor cell surface. © 1990.