Malignancy kallikreins

Sequence changes, including polymorphisms and mutations, are clinically important. In addition to medicolegal applications, they can also be indicators for susceptibility and prognosis for different malignancies [52]. KLK3 is the most extensively studied kallikrein in this respect. Comparison of the... 

In recent RT-PCR studies, many kallikreins have been proposed as new biomarkers for malignancies other than prostate cancer. Breast, ovarian, and testicular cancers are the most studied. Certain kallikreins were found to be differentially expressed in various malignancies (up- or downregulated), and the increase or decrease of their expression may be associated with prognosis [43, 58, 70, 89-94]. We have immunohistochemically evaluated some kallikreins in malignant diseases, including two series of prostate and renal cell carcinoma, and have examined their prognostic values [84, 85]. 

In malignancy, glandular epithelia constitute the main kallikrein immunoex-pression sites, and staining of their secretions indicating that these proteases are secreted. Similar to the IE pattern in normal glandular tissues, all hKs are expressed in adenocarcinomas. In the future, it is clearly worthwhile to study the relation of the IE of all hKs with prognosis of several malignancies and to correlate these results with those obtained by other methods. 

With the identification and characterization of all members of the kallikrein gene family, accumulating evidence indicates that other kallikreins might be also related to hormonal (e.g., breast, prostate, testicular, and ovarian cancers) and other malignancies. KLK6 and KLK10 were originally isolated by differential display from breast cancer libraries [216],... 

Several mechanisms can be proposed by which kallikreins can be involved in the pathogenesis of endocrine-related malignancies. Proteolytic enzymes are thought to be involved in tumor progression because of their role in extracellular matrix degradation. Many studies have shown that a variety of proteolytic enzymes are overproduced either by the cancer cells themselves or by the surrounding stromal cells, and that their overexpression is associated with unfavorable clinical prognosis [249],... 

Breast, prostate, testicular, and ovarian cancers are all considered hormonal malignancies. Sex hormones are known to affect the initiation or progression of these malignancies. However, all kallikreins are under sex steroid hormonal regulation. Taken together, kallikreins may represent downstream targets by which hormones affect the initiation or progression of such tumors. 

Petraki CD, Gregorakis AK, Papanastasiou PA, Karavana VN, Luo LY, Diamandis EP. Immunohistochemical localization of human kallikreins 6, 10 and 13 in benign and malignant prostatic tissues. Prostat CancerProstatic Dis 2003 6 223-227. 

Magklara A, Scorilas A, Stephan C, et al. Decreased concentrations of prostate-specific antigen and human glandular kallikrein 2 in malignant versus nonmalignant prostatic tissue. Urology 2000 56 527-532. 

We demonstrated that BK is an important mediator of EPR effect in cancer [36]. Figure 5 shows network of BK and other mediators involving in EPR effect. BK interacts with various proinflammatory factors involving vascular permeability. For instance, it is also known to activate endothelial cell-type nitric oxide synthase (eNOS), which is one of the primary enzymes to produce NO from L-arginine. We have reported that the BK-generating cascade is activated in tumor tissues [36]. More importantly, malignant ascetic and pleural fluids would be caused by activation of kallikrein-kinin system in carcinomatosis [37]. 

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