Modulation of the plasminogen activation system by inflammatory cytokines in human colon carcinoma cells.
Inflammation may promote malignant invasion by enhancing cancer cell-associated proteolysis. Here we present the effect of inflammatory cytokines on the plasminogen activation system of eight human colon carcinoma cell lines. Tumour necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) increased in several, but not all, cell lines the production of urokinase-type plasminogen activator (uPA), tissue-type PA (tPA) and plasminogen activator inhibitor type 1 (PAI-1) as analysed by zymography, enzyme immunoassays and Northern analysis. Interleukin 6 (IL-6) had no effect. uPA receptor (uPAR) mRNA levels were also upregulated. However, each individual cell line responded differently following exposure to TNF-alpha or IL-1 beta. For example, there was a dose-dependent up-regulation of uPA and PAI-1 in SW 620 cells, whereas increased uPA production in SW 1116 cells was not accompanied by an increase in PAI-1. The TNF-alpha stimulatory effect was blocked by anti-TNF-alpha Fab fragments. All cell lines expressed both types of TNF receptor mRNAs, whereas no transcript for TNF-alpha, IL-1 beta, IL-6, IL-6 receptor or the IL-1 receptors was found. Our results demonstrate that TNF-alpha and IL-1 beta stimulate the plasminogen activation system in tumour cell but the responses differed even in cells derived from the same tissue origin.
Trân-Thang
C
C
Swiss Institute for Experimental Cancer Research (ISREC), Epalinges, Switzerland.
Kruithof
E
E
Lahm
H
H
Schuster
W A
WA
Tada
M
M
Sordat
B
B
D015152:Blotting, Northern; D003110:Colonic Neoplasms / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis*; D010960:Plasminogen Activators / Q000096:biosynthesis*; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D017395:Plasminogen Activator Inhibitor 1; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D010960:Plasminogen Activators