Tumor Cell Interactions with Elastin: Implications for Pulmonary Metastasis

Elastin surrounds microvessels in the pulmonary circulation and may pose a barrier to the extravasation of metastatic tumor cells. We find that lung-colonizing murine melanoma cells produce an enzymatic activity that degrades elastin. In addition, the elastin fragments liberated by enzymatic digestion of insoluble elastin stimulate tumor cell chemotaxis. Chemotactic activity is associated with other forms of soluble elastin, including alpha-elastin and tropoelastin. Val-Gly-Val-Ala-Pro-Gly, a synthetic peptide that is a repeat sequence in the elastin molecule, also displayed tumor cell chemotactic activity. The ability to degrade elastin and to migrate in response to soluble elastin peptides is not a property of all tumor cells, but it is most commonly found associated with metastatic tumor cells that colonize pulmonary tissue. We postulate that the ability to migrate in response to elastin fragments may facilitate tumor cell invasion of elastin-rich pulmonary tissue.