The tumor-associated antigen 90K/Mac-2-binding protein secreted by human colon carcinoma cells enhances extracellular levels of promatrilysin and is a novel substrate of matrix metalloproteinases-2, -7 (matrilysin) and -9: Implications of proteolytic cleavage

• Published in: Biochimica et biophysica acta Vol. 1800; no. 3; pp. 336 - 343
• Main Authors: Ulmer, Tricia A., Keeler, Vicki, André, Sabine, Gabius, Hans-Joachim, Loh, Lambert, Laferté, Suzanne
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2010
• Subjects: Antigens, Neoplasm - isolation & purification; Antigens, Neoplasm - metabolism; Biomarkers, Tumor; Cell Line, Tumor; Colon cancer; Colonic Neoplasms - pathology; Colonic Neoplasms - secretion; Enzyme Precursors - metabolism; Galectin-3; Humans; Kinetics; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 7 - metabolism; Matrix Metalloproteinase 9 - metabolism; Matrix metalloproteinases; Membrane Glycoproteins - isolation & purification; Membrane Glycoproteins - metabolism; Membrane Glycoproteins - secretion; Metalloendopeptidases - metabolism; Peptide Fragments - isolation & purification; Peptide Fragments - metabolism; Prognosis; Recombinant Proteins - isolation & purification; Recombinant Proteins - metabolism; Substrate Specificity; Tumor-associated antigen 90K; Vaccinia virus - genetics; PBS; Matrix metalloproteinases; IgG; TAA90K; Galectin-3; EDTA; IL-1β; ECM; IL-6; BSA; DMEM; MMP; SDS-PAGE; Tumor-associated antigen 90K; Colon cancer; CyCAP; MEM; FBS; PBST; APMA; HPLC; ELISA
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2009.07.030

The tumor-associated antigen 90K (TAA90K)/Mac-2-binding protein is expressed at elevated level in cancerous tissues and associated with poor prognosis. Since TAA90K has been implicated in the restructuring of the extracellular matrix, we examined the functional relationship between colon cancer cell-derived TAA90K and the matrix metalloproteinase (MMP) promatrilysin (proMMP-7), and also tested whether TAA90K is a novel substrate for MMPs-2, -7 and -9. The effect of TAA90K on proMMP-7 levels in HT-29 conditioned media was quantified by enzyme-linked immunosorbent assays. Binding of TAA90K to MMPs, extracellular matrix proteins and galectin-3 was measured by solid-phase binding assays. Proteolytic cleavage of TAA90K by MMPs was documented by SDS-PAGE and protein sequencing analysis. TAA90K enhanced extracellular levels of proMMP-7 in HT-29 cells. In addition, TAA90K was cleaved by MMPs-2, -7 and -9. MMP-7-mediated cleavage of TAA90K did not affect its binding to MMP-7, laminin-1, collagen IV and galectin-3 but reduced its interaction with fibronectin and laminin-10, and lowered the levels of proMMP-7 in the HT-29 medium. TAA90K is a novel substrate for MMPs-2, -7 and -9 and modulates proMMP-7 levels in colon cancer cells. Proteolytic cleavage of TAA90K may have functional implications in colon cancer.