Tumor cell invasion, a key step in the metastatic process, involves a complex series of correlated macromolecular interactions. These include interaction with, and movement through, collagen, most often type I and/or basement membrane (type IV) collagen. In general, invasion of the basement membrane is believed to be a critical step in the metastatic process. Human melanoma cells have been shown to bind distinct triple-helical regions within type IV collagen (1-5). Melanoma receptors for triple-helical collagen fall into one of two categories: members of the integrin heterodimeric protein family (␣ 1 ␤ 1 , ␣ 2 ␤ 1 , and ␣ 3 ␤ 1 integrins) or cell surface proteoglycans (such as CD44 and melanoma-associated proteoglycan/melanoma chondroitin sulfate proteoglycan (MPG/MCSP/NG2)).