title: Clinicopathological characteristics of androgen-dependent advanced prostate             cancer patients with α2-macroglobulin deficiency.
abstract: α2-Macroglobulin (α2M) is thought to be involved in cancer metastasis and inflammatory reaction through its functions as a proteinase inhibitor and carrier protein for interleukin-6 (IL-6). We previously reported that advanced prostate cancer (PCa) patients with multiple distant bone metastases had markedly decreased serum α2M levels (<20 mg/dl) and no detection of α2M by immunoelectrophoresis (defined as α2M deficiency). We also showed a relationship between serum α2M levels and acute inflammatory biomarkers in PCa patients with or without α2M deficiency. In this study, we analyzed in detail the clinicopathological characteristics and pathogenesis of α2M deficiency in androgen-dependent advanced PCa patients. In this study, 15 PCa patients were diagnosed at the Kitasato University Hospital. α2M levels were determined by laser-nephelometry and immunoelectrophoresis, and PSA levels were determined by enzyme immunoassay. IL-6 levels were measured by a specific luminescence sandwich-type enzyme-linked immunosorbent assay, and CRP levels were determined by latex nephelometry. Immunohistochemical staining for PSA in PCa specimens was also performed. The binding assay for purified α2M and PSA was analyzed by western blotting. α2M deficiency was specific for advanced PCa patients with multiple distant bone metastases. PSA was markedly detected in sera and prostate specimens of advanced PCa patients with α2M deficiency, and there was a negative correlation between serum α2M and PSA levels during the course of clinical treatment. Acute inflammatory biomarkers such as IL-6 and CRP were within reference range in α2M-deficient patients. The binding assay showed that PSA easily bound to α2M, which was detected as an approximately 800-kDa complex by western blotting. Further, genetic analysis of a α2M-deficient patient showed no mutations in the α2M gene. These results suggested that α2M deficiency develops from catabolism of α2M in androgen-dependent advanced PCa patients, and serum α2M level may be an indicator of PCa disease progression in addition to PSA level.
authors.affiliation: Department of Laboratory Medicine, School of Medicine, Kitasato University, 1-15-1 Kitasato, Sagamihara, Minami-ku, Kanagawa 252-0374, Japan. kanoh@med.kitasato-u.ac.jp
authors.forename: Yuhsaku
authors.initials: Y
authors.lastname: Kanoh
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohtani
authors.forename: Shin
authors.initials: S
authors.lastname: Egawa
authors.forename: Shiro
authors.initials: S
authors.lastname: Baba
authors.forename: Tohru
authors.initials: T
authors.lastname: Akahoshi
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D001842:Bone and Bones / Q000000981:diagnostic imaging; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology; D011877:Radionuclide Imaging; D017422:Sequence Analysis, DNA; D000511:alpha-Macroglobulins / Q000172:deficiency* / Q000235:genetics
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D000511:alpha-Macroglobulins; D002097:C-Reactive Protein; D017430:Prostate-Specific Antigen