Distribution of 15 Human Kallikreins in Tissues and Biological Fluids

Abstract

Background: Kallikreins (KLKs) are a group of 15 secreted serine proteases. Some KLKs are established or candidate cancer biomarkers, but for most the physiological function is unknown. We characterized the protein and mRNA abundance patterns of all 15 KLKs in multiple panels of human tissues and biological fluids. Methods: We used sensitive and specific sandwich-type ELISAs for each KLK. Reverse transcription PCR was used for transcript amplification. Multiple panels of human tissue extracts (adult and fetal) were tested, along with various biological fluids. Results: Quantitative protein expression data on 7 sets of adult and 3 sets of fetal tissues were collected for all 15 KLKs. KLKs were also quantified in the following biological fluids: seminal plasma, breast milk, follicular fluid, breast cyst fluid, breast cancer cytosol, amniotic fluid, ovarian cancer ascites, cerebrospinal fluid, cervicovaginal fluid, and urine. The data were used to generate heat maps of KLK concentrations in tissues and fluids and categorize KLK abundance as highly restricted (KLK2 and KLK3 in prostate), restricted (KLK5 in skin, salivary gland, breast, and esophagus; KLK6 in brain and central nervous system; KLK7 in esophagus, heart, liver, and skin; KLK8 in breast, esophagus, skin, and tonsil; KLK13 in esophagus and tonsil), or wide (KLKs 1, 4, 9, 10, 11, 12, 14, and 15). Conclusions: Quantitative KLK concentrations in tissues and fluids aid in the elucidation of KLK function, and coexpression patterns provide clues for KLK participation in proteolytic cascades.