Association of interleukin-8 and plasminogen activator system in the progression of colorectal cancer.
The aim of this study was to investigate the relationship of Interleukin-8 (IL-8) with vascular endothelial growth factor (VEGF) and plasminogen activator system (PA system) in the progression of colorectal cancer (CRC). In eighty-seven patients with CRC, the levels of IL-8, and VEGF as representative angiogenic factors and urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), and PAI-2 as representative invasive factors were quantitatively assayed in tumor and adjacent normal tissues. The levels of IL-8, VEGF, and PA system factors in tumor tissues were all significantly higher than those in normal tissues. The IL-8 level was significantly associated with tumor size, depth of infiltration, Dukes stage, and liver metastasis, and also significantly correlated with the levels of VEGF, uPAR, uPA, and PAI-1. The VEGF level was significantly associated with tumor size, vascular involvement. The levels of uPAR and PAI-1 were significantly associated with tumor size and depth of infiltration, and the uPAR level was associated with liver metastasis. The VEGF level was significantly correlated with the levels of uPAR and PAI-1. These results reveal that IL-8, VEGF, and PA system factors are contributed to tumor growth, invasion, and metastasis in CRC. Univariate analysis revealed that high levels of IL-8, VEGF, and uPAR were significantly associated with a shorter overall survival time; however, multivariate analysis identified only liver metastasis as an independent prognostic factor. In conclusion, IL-8 is responsible to tumor progression and liver metastasis of CRC, and the activation of PAS induced by IL-8 as well as VEGF may play an important role in the progression of CRC.
Terada
H
H
Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan. terap@hamamatsu-kb.or.jp
Urano
T
T
Konno
H
H
D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000378:metabolism*; D008113:Liver Neoplasms / Q000556:secondary; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D010960:Plasminogen Activators / Q000378:metabolism*; D011336:Probability; D011379:Prognosis; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D016209:Interleukin-8; D042461:Vascular Endothelial Growth Factor A; D010960:Plasminogen Activators