Expression of urokinase‐type plasminogen activator and plasminogen activator inhibitor in colon disease

Abstract

Surveillance colonoscopy and biopsy are inaccurate methods of predicting the likelihood of ulcerative colitis patients to develop colon carcinoma. We examined uPA and PAI-1 as potential markers for assessing these patients and those with familial polyposis who are at risk of developing colon cancer. For comparison, biopsies of normal colon and Crohn's disease were evaluated. We examined 77 colonic mucosa specimens taken from patients undergoing elective resection for benign and malignant colonic disease. uPA and PAI-1 were measured using a monoclonal antibody-based ELISA kit (American Diagnostica, Greenwich, CT) and expressed as ng/mg extract protein. Intra- and interassay controls of uPA gave CV = 3-4% and CV = 8-9%, respectively, while those for PAI-1 were 6-7% and 10-11%, respectively. The Mann-Whitney test showed that both uPA and PAI-1 expression were significantly higher in colon cancer, chronic ulcerative colitis, and Crohn's disease than in normal colon. uPA in familial polyposis samples was similar to that of normal colon, while PAI-1 was much lower than in normal colon. Neither patient age nor sex appeared to influence the expression of these potential markers in any tissue. The pattern of uPA and PAI-1 expression in normal, benign and malignant colon suggests these proteins deserve further consideration as markers for assessing colon carcinoma risk.

The Effects of Cyclooxygenase2–ProstaglandinE2 Pathway on Helicobacter pylori‐Induced Urokinase‐Type Plasminogen Activator System in the Gastric Cancer Cells

“…These reports indicated that H. pylori infection may play a role in destruction of the extracellular matrix. uPA and uPAR are reportedly produced by the cancer cells and stromal cells in several types of human tumors in vivo and in vitro [9–12], and play an important role in the process of degradation of the extracellular matrix [4–6]. The secreted uPA binds to uPAR on the cell membrane of some types of cells to restrict the uPA activity to the cell surfaces.…”

Differential Prognostic Impact of uPA and PAI-1 in Colon and Rectal Cancer

“…Earlier studies indicate that MMP-9 and uPAR expression in tumour-associated lymphocytes, macrophages and neutrophils are inversely associated with invasion and metastasis [41] . It is also reported that inflammatory conditions in the colon is associated with an increased uPA expression [42,43] . These observations could also in part explain the findings in the present study, as tumourassociated lymphocytes are suspected to exert anticancer effects [44] .…”

Angiogenesis in inflammatory bowel disease

“…Besides MMP-3 and MMP-9 are markedly up-regulated in intestinal fistulae, that may contribute to fistula formation and perpetuation through degradation of the extracellular matrix [43]. Moreover, both uPA and plasminogen activator inhibitor; (PAI-1) expressions are significantly higher in IBD patients than in controls [44]. uPA and plasmin, in addition to their role in fibrinolysis and activation of pro-MMPs, have been shown to be an intracellular signal transducer through specific receptors Therefore, the uPA/ plasmin system has been shown to play an important role in pathological angiogenesis.…”