Human kallikrein 11: a new biomarker of prostate and ovarian carcinoma.
Human kallikrein 11 (hK11) is a putative serine protease of the human kallikrein gene family. Currently, no methods are available for measuring hK11 in biological fluids and tissues. Our aim was to develop immunological reagents and assays for measuring hK11 and examine if the concentration of this kallikrein is altered in disease states. We produced recombinant hK11 protein in a baculovirus system and used it to develop monoclonal and polyclonal antibodies against hK11. We then developed an immunofluorometric procedure for measuring hK11 in biological fluids and tissue extracts with high sensitivity and specificity. We further quantified hK11 in various biological fluids and in serum of patients with various cancers. The hK11 immunofluorometric assay is highly sensitive (detection limit, 0.1 microg/l) and specific (no detectable cross-reactivity for other homologous kallikreins). We established the tissue expression pattern of hK11 at the protein level and found the highest levels in the prostate, followed by stomach, trachea, skin, and colon. We have immunohistochemically localized hK11 in epithelial cells of various organs. We further detected hK11 in amniotic fluid, milk of lactating women, cerebrospinal fluid, follicular fluid, and breast cancer cytosols. However, highest levels were seen in prostatic tissue extracts and seminal plasma. hK11 in seminal plasma and prostatic extracts is present at approximately 300-fold lower levels than prostate-specific antigen and at approximately the same levels as hK2. hK11 expression in breast cancer cell lines is up-regulated by estradiol. Elevated serum levels of hK11 were found in 70% of women with ovarian cancer and in 60% of men with prostate cancer. This is the first reported immunological assay for hK11. Analysis of this biomarker in serum may aid in the diagnosis and monitoring of ovarian and prostatic carcinoma.
Diamandis
Eleftherios P
EP
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5 Canada. ediamandis@mtsinai.on.ca
Okui
Akira
A
Mitsui
Shinichii
S
Luo
Liu-Ying
LY
Soosaipillai
Antoninus
A
Grass
Linda
L
Nakamura
Terukazu
T
Howarth
David J C
DJ
Yamaguchi
Nozomi
N
D000653:Amniotic Fluid / Q000201:enzymology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology; D016367:Baculoviridae / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D007610:Kallikreins / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008895:Milk, Human / Q000201:enzymology; D010051:Ovarian Neoplasms / Q000201:enzymology*; D011247:Pregnancy; D011471:Prostatic Neoplasms / Q000201:enzymology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D012661:Semen / Q000201:enzymology
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D011994:Recombinant Proteins; D007610:Kallikreins