Since the adhesive interaction between
tumor cells and host cells, or extracellular matrix (ECM), presumably plays a crucial role in metastatic formation during a series of complex events, we used synthetic or recombinant
polypeptide analogues,
poly(RGD) or CH-271-based on
Arg-Gly-Asp(RGD) sequence or functional domains in
fibronectin. Use of these analogues regulated the mechanisms involved in cell adhesion during the metastatic process.
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 B-16-BL6
melanoma, multiple administrations of this
polypeptide, before or after surgical excision of the primary
tumor, resulted in significant inhibition of
tumor metastasis without affecting the growth of the primary
tumor. Further, it substantially prolonged the survival time of mice. The mechanism responsible for the inhibition of
tumor metastasis by the
polypeptides is partly associated with the ability to interfere with cell functions such as adhesiveness, motility, and invasiveness in the cellular adhesive process of
metastasis. The combination of CH-271 fusion
polypeptide and anticancer drugs, i.e., anti-adhesion
therapy and
chemotherapy, caused a dramatic inhibition of lung and liver
metastasis of
tumors when compared with either treatment alone, or in the control. Since the
polypeptides derived from
cell adhesion molecules showed no short-term toxicity to the host, they may provide a promising approach for the control of
cancer metastasis.