Echistatin, a low molecular weight, RGD-containing
protein isolated from the
venom of Echis carinatus, inhibited
Lewis lung carcinoma cell (3LL) adhesion to immobilized
fibronectin and
laminin. The inhibition was specific, noncytotoxic, dose-dependent and fully reversible.
Echistatin showed a stronger activity in inhibiting cell adhesion to
fibronectin rather than to
laminin and it resulted about 3-fold more effective than
kistrin, an other ROD-
snake venom protein, in inhibiting 3LL cell attachment to both substrates. The ability of
echistatin to modulate experimental
metastasis formation in vivo was also evaluated. A 20% inhibition of the lung
metastasis spread with respect to controls was observed when 3LL cells and
echistatin were coinjected i.m. into male C57BL/6NCr1BR mice. When
echistatin was administered i.p. 1 mu g/g of
body weight/72 h x 4 doses into mice bearing
Lewis lung carcinoma, it promoted only a 15% inhibition of
tumor growth but inhibited by 45% lung
metastasis formation. These results demonstrate that
echistatin is able to inhibit
metastasis attachment and spreading in experimental system in vivo independently by its effect on the primary
tumor.