Heterologously overexpressed, affinity-purified human meprin α is functionally active and cleaves components of the basement membrane in vitro

Meprins are astacin-like metalloproteases of renal and intestinal epithelia and embryonic neuroepithelial cells. The full length cDNA of the human meprin α subunit has been overexpressed in baculovirus-infected insect cells yielding the tetrameric proprotein which could be proteolytically activated and affinity-purified to homogeneity. Recombinant meprin α hydrolyzes the synthetic substrate N-benzoyl-tyrosyl- p-aminobenzoic acid (PABA-peptide) and cleaves by limited proteolysis the basement membrane constituents laminin 1 and laminin 5. This supports a concept that meprin α, when basolaterally secreted by human colon carcinoma epithelial cells, increases the proteolytic capacity for tumor progression in the stroma.