title: Interaction of plasminogen with dipeptidyl peptidase IV initiates a signal transduction mechanism which regulates expression of matrix metalloproteinase-9 by prostate cancer cells.
abstract: Both plasminogen (Pg) activation and matrix metalloproteinases (MMPs) are involved in the proteolytic degradation of extracellular matrix components, a requisite event for malignant cell metastasis. The highly invasive 1-LN human prostate tumour cell line synthesizes and secretes large amounts of Pg activators and MMPs. We demonstrate here that the Pg type 2 (Pg 2) receptor in these cells is composed primarily of the membrane glycoprotein dipeptidyl peptidase IV (DPP IV). Pg 2 has six glycoforms that differ in their sialic acid content. Only the highly sialylated Pg 2gamma, Pg 2delta and Pg 2epsilon glycoforms bind to DPP IV via their carbohydrate chains and induce a Ca(2+) signalling cascade; however, Pg 2epsilon alone is also able to significantly stimulate expression of MMP-9. We further demonstrate that the Pg-mediated invasive activity of 1-LN cells is dependent on the availability of Pg 2epsilon. This is the first demonstration of a direct association between the expression of MMP-9 and the Pg activation system.
authors: Department of Pathology, Box 3712, Duke University Medical Center, Durham, NC 27710, USA. gonza002@mc.duke.edu
authors: M
authors: M
authors: Gonzalez-Gronow
authors: H E
authors: HE
authors: Grenett
authors: M R
authors: MR
authors: Weber
authors: G
authors: G
authors: Gawdi
authors: S V
authors: SV
authors: Pizzo
mesh_terms: D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D017931:DNA Primers; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D010958:Plasminogen / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D011485:Protein Binding; D014407:Tumor Cells, Cultured
chemical_list: D017931:DNA Primers; D010958:Plasminogen; D018819:Dipeptidyl Peptidase 4; D020780:Matrix Metalloproteinase 9; D002118:Calcium