Since the adhesive interaction between
tumor cells and host cells, or extracellular matrix (ECM), presumably plays a crucial role in metastatic formation, we used synthetic or recombinant
polypeptide analogues,
poly (RGD), CH-271 or
SCM-chitin-RGDS based on
Arg-Gly-Asp (RGD) sequence.
Poly (RGD) effectively inhibited the experimental lung and liver
metastasis when coinjected i.v. with different types of
tumors. In a spontaneous lung
metastasis model using B16-BL6
melanoma, multiple administrations of this
polypeptide, before or after surgical excision of the primary
tumor, resulted in significant inhibition of
tumor metastasis. The mechanism responsible for the inhibition is partly associated with the ability to interfere with cell functions such as adhesiveness, motility, and invasiveness in the process of
metastasis. CH-271 fusion
polypeptide was much more effective in inhibiting lung or liver
metastasis of
tumors than cell-binding domain (C-274) or
heparin-binding domain (H-271)
polypeptides.
SCM-chitin-RGDS conjugate significantly reduced the number of
tumor colonies in the lungs by coinjection with Colon 26
carcinoma as compared with either RGDS or
SCM-chitin alone. Since the
polypeptides derived from
cell adhesion molecules showed no toxicity to the host, they may provide a promising approach for the control of
cancer metastasis.