ISOLATION, PURIFICATION, AND CHARACTERIZATION OF A COLLAGEN-ASSOCIATED SERPIN, CASPIN, PRODUCED BY MURINE COLON ADENOCARCINOMA CELLS

A 45-kDa serpin secreted by a murine colon adenocarcinoma cell line, c olon26, was isolated, purified, and characterized, It was found to bin d specifically to type I collagen with high affinity and to type III c ollagen with lower affinity, Immunohistochemical studies of murine emb ryonic tissues showed a specific distribution of this collagen-associa ted serpin, named caspin, in relation to the formation of bone, cartil age, teeth, and basement membrane. The expression of caspin in high an d low lung metastatic subclones of colon26 cell lines was inversely co rrelated with their metastatic capacity: low lung metastatic cells sec reted higher amounts of caspin than their high lung metastatic counter parts. Caspin also demonstrated high homology with human pigment epith elium-derived factor/early population doubling level cDNA-1, which rep ortedly induces neuronal differentiation of human retinoblastoma cells and is expressed in association with G(0) growth arrest. These findin gs suggest that caspin/pigment epithelium-derived factor/early populat ion doubling level cDNA-1 is a novel factor that might play a crucial role in embryogenesis and tumor metastasis through binding to the extr acellular matrix.