Plasminogen activator inhibitor-1 as a potential marker for the malignancy of colorectal cancer

Sakakibara, Tetsuo; Hibi, Kenji; Koike, Masahiko; Fujiwara, Michitaka; Kodera, Yasuhiro; Ito, Katsuki; Nakao, Akimasa

doi:10.1038/sj.bjc.6602743

Cited by 59 publications

(44 citation statements)

References 27 publications

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“…An increased uPA, uPAR, PAI 1 and PAI 2 expression in tumor tissue was confirmed in a number of tumors, such as breast, ovarian, kidney and stomach [26][27][28][29][30][31][32] and it is certain that these factors play an important role in tumor invasiveness and metastasizing.…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of the plasminogen activator system in relation to grade of tumor and treatment response in colorectal carcinoma patients

Halámková

Kiss²,

Pavlovský³

et al. 2011

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Urokinase (uPA) plays an essential role in the activation of plasminogen to plasmin, and together with its receptor (uPAR), tissue activator (tPA) and urokinase inhibitors (PAI 1, PAI 2, PAI 3 and protease nexin) forms the plasminogen activator system (PAS), a component of metastatic cascade importantly contributing to the invasive growth and angiogenesis of malignant tumours. In our project we examined the expression of uPA, uPAR, PAI 1 and PAI 2 in tumor tissue and we also studied the plasma levels of PAI 1 before and after the initiation of therapy in patients with colorectal carcinoma in relationship to grade of tumor and the treatment response. In our prospective evaluation we included 80 patients treated for adenocarcinoma of the colon and rectum. Analysis of collected data revealed statistically significant evidence of a relationship between the level of PAI 1 in plasma before treatment and grade of the tumor, which increases with tumor grade (p=0.025). We demonstrated that there exists a statistically significant relationship between the expression of PAI 2 (p<0.001) and uPAR (p=0.031) and grade of tumor. We also confirmed a statistically significant relationship between soluble levels of PAI 1 before treatment and therapeutic response (p=0.021). In our group of patients the expression of uPA, uPAR, PAI 1 and 2 in tumor tissue in relation to response to treatment was also assessed. Our results suggest that the greater expression of these parameters in tumor tissue is linked to a worse response to therapy. In conclusion, PAS factors help as a prognostic indicators and could also act as a predictive factor in colorectal carcinoma.

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Section: Discussionmentioning

confidence: 99%

Clinical significance of the plasminogen activator system in relation to grade of tumor and treatment response in colorectal carcinoma patients

Halámková

Kiss²,

Pavlovský³

et al. 2011

neo

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“…Overexpression of PAI-1 has been found in many obesity-related types of cancer and is associated with the progression of breast, endometrial, colorectal, thyroid, renal, and prostate cancer (97)(98)(99)(100)(101)(102). In addition to autocrine production by tumor cells, systemic levels of PAI-1 (e.g., produced by immune cells or adipocytes in obesity) appear to be essential for its tumor-promoting effects, though level dependent (103).…”

Section: Adipokinesmentioning

confidence: 99%

Obesity and Cancer: The Role of Dysfunctional Adipose Tissue

Kruijsdijk

Wall

Visseren

2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Overweight and obesity are health problems of epidemic proportions, increasing the risk not only of cardiovascular disease and type 2 diabetes mellitus but also of various types of cancer. Obesity is strongly associated with changes in the physiological function of adipose tissue, leading to insulin resistance, chronic inflammation, and altered secretion of adipokines. Several of these factors, such as insulin resistance, increased levels of leptin, plasminogen activator inhibitor-1, and endogenous sex steroids, decreased levels of adiponectin, and chronic inflammation, are involved in carcinogenesis and cancer progression. This article reviews these mechanisms, focusing on adipose tissue dysfunction as a unifying causal factor. Although understanding of the link between obesity and cancer might provide therapeutic targets, preventing overweight and obesity still remains number one priority. (Cancer Epidemiol

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“…Finally, we demonstrated that PAI-1 expression was significantly correlated with a poor prognosis in esophageal squamous cell carcinoma and colorectal cancer. (24,25) These results prompted us to examine the PAI-1 expression level in other cancers, especially in gastric cancer.To test the hypothesis that PAI-1 may serve as a candidate marker for malignancy in gastric cancer, we carried out a quantitative RT-PCR and evaluated the relationship between PAI-1 gene expression levels and clinicopathological findings in gastric cancer. …”

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confidence: 99%

Plasminogen activator inhibitor‐1 as a potential marker for the malignancy of gastric cancer

et al. 2006

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To test the hypothesis that plasminogen activator inhibitor-1 (PAI-1) may serve as a candidate marker for the malignancy of gastric cancer, we carried out quantitative reverse transcriptionpolymerase chain reaction for the PAI-1 gene and evaluated the possible relationship between PAI-1 gene expression levels and clinicopathological findings in gastric cancer. A significant increase in PAI-1 expression scores was observed in lymph node metastasis-positive gastric cancers (2.11 ± ± ± ± 0.35) compared to metastasis-negative cancers (0.33 ± ± ± ± 0.49) (P = 0.0048), as well as in distant metastasis-positive gastric cancers (3.68 ± ± ± ± 0.58) compared to metastasis-negative cancers (1.20 ± ± ± ± 0.32). The PAI-1 expression score markedly increased with tumor stage (P < 0.0001; ANOVA test). Moreover, multivariate analysis revealed the PAI-1 expression score to be a strong and independent prognostic factor for gastric cancer (P = 0.0450). These results suggested that PAI-1 might serve as a new and promising parameter for the prediction of prognosis in gastric cancer. G astric cancer is one of the most common malignancies worldwide. (1) Though the prognosis of this cancer has improved in recent years, many patients still die from it. Therefore, the identification of precise prognostic markers and effective therapeutic targets is pivotal in the treatment of gastric cancer. Accumulating evidence indicates that gastric cancer is the result of various genetic and epigenetic alterations of oncogenes, tumor suppressor genes, DNA repair genes, cellcycle regulators and cell adhesion molecules. (2) DNA hypermethylation has been particularly well studied and is found in the CpG islands of several genes. In gastric cancer, the inactivation of hMLH1, MGMT, TIMP-3 and p16 by promoter hypermethylation has been demonstrated. (3)(4)(5)(6) Destruction of the extracellular matrix and basement membrane is essential for tumor invasion and metastasis. The extracellular matrix is degraded by extracellular proteolytic enzymes such as metalloproteases and serine proteases. (7) PAI-1, a 45-kDa serine protease inhibitor with a reactive peptide bond (Arg 345 -Met 346 ), is a multifaceted proteolytic inhibitor that not only functions as a fibrinolytic inhibitor, but also plays an important role in signal transduction, cell adherence and cell migration. (8,9) A possible promoting function of PAI-1 in tumor growth is suggested by its potential to modify cell adhesion capacity, which is independent of uPA inhibitory activity. (10) Angiogenesis, the formation of new capillaries from existing blood vessels, is essential for the growth of a solid tumor. (11) Many studies have shown that malignant tumors depend on angiogenesis for their growth and metastasis. (12) Recently, a role of the PA system in tumor angiogenesis has been demonstrated, supporting the idea that PAI-1 is a key factor in angiogenesis. (13) Plasminogen activator inhibitor-1 is a clinical marker for poor prognosis in several human cancers. (14)(15)(16)(17)(18) Recently, Kaneko et al. ...

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Plasminogen activator inhibitor-1 as a potential marker for the malignancy of colorectal cancer

Cited by 59 publications

References 27 publications

Clinical significance of the plasminogen activator system in relation to grade of tumor and treatment response in colorectal carcinoma patients

Clinical significance of the plasminogen activator system in relation to grade of tumor and treatment response in colorectal carcinoma patients

Obesity and Cancer: The Role of Dysfunctional Adipose Tissue

Plasminogen activator inhibitor‐1 as a potential marker for the malignancy of gastric cancer

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