neural crest cell cultures (Maxwell and Forbes, 1987), and exocrine acinar epithelial cells (Oliver et al., 1987). Similar results were obtained when primary normal human prostate cells were cultured in EHS (Fong et al., 1991). The concept that certain components of the matrix were regulating cell morphogenesis and differentiation was palpable; the question that remained was, what is the exact mechanism? In 1990, further evidence suggested that matrix components were interacting with response elements in the nucleus (Schmidhauser et al., 1990, 1992; Myers et al., 1998). Simultaneously Streuli and Bissell (1990) demonstrated that the appearance of milk protein after collagen gels were floated was concomitant with formation of an endogenous basement membrane in primary mammary cells. The first evidence that the ECM, through direct interaction with integrins, was regulating gene expression and differentiation came in 1991 when Streuli et al. (1991) embedded single mammary cells inside a laminin-rich ECM. They showed that these cells were able to synthsize β-casein when laminin was present, but treatment with an anti–β1 integrin antibody would prevent expression of the milk protein. Further studies determined that pure laminin-111, but not other ECM components, directs the expression of the β-casein gene through reporter assays (Streuli et
