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Changes of Proteases and Proteinase Inhibitors in Androgen-dependent Advanced Prostate Cancer Patients with α2-Macroglubin Deficiency by Yuhsaku Kanoh, Hideki Ohtani, Shin Egawa, Shiro Baba, Tohru Akahoshi

Background: It is thought that the quantitative imbalance between proteases and their inhibitors is a causative factor in invasion and metastasis of cancer cells. We previously reported on a number of androgen-dependent advanced prostate cancer (PCa) patients in which serum α2-macroglobulin (α2M) levels were markedly decreased to <20 mg/dL (defined as α2M deficiency). Anti-androgen therapy is at first generally very effective for androgen-dependent advanced PCa, yielding survival benefits for most patients. In the present study, we evaluated serum levels of PSA, matrix metalloproteinases-2 (MMP-2), α2M, and α2-plasmin inhibitor (α2PI) in advanced PCa patients with or without α2M deficiency in order to determine the clinical significance of these proteases and proteinase inhibitors for PCa progression.
Methods: In this study, 33 PCa patients were diagnosed at the Kitasato University Hospital and compared with 10 healthy controls. PSA and MMP-2 levels were determined by enzyme immunoassay. Measurement of α2M was performed by laser-nephelometry. α2PI levels were determined by turbidimetric immunoassay.
Results: Serum levels of PSA and MMP-2 in PCa patients with α2M deficiency were significantly higher than in patients not α2M-deficient. In contrast, serum levels of α2M and α2PI in these patients were significantly lower than in those not α2M-deficient. PSA and α2M levels showed an inverse relationship in androgen-dependent advanced PCa with α2M deficiency.
Conclusions: Our findings indicate that the serum levels of these proteases and proteinase inhibitors, which are involved in the invasion and metastasis of PCa, may be indicators of PCa disease progression in addition to PSA levels.

DOI: Clin. Lab. 2012;58:217-225