Immunofluorometric assay of human kallikrein 6 (zyme/protease M/neurosin) and preliminary clinical applications

Diamandis, Eleftherios P.; Yousef, George M.; Soosaipillai, Antoninus; Grass, Linda; Porter, Alfred W.; Little, Sheila P.; Sotiropoulou, Georgia

doi:10.1016/s0009-9120(00)00145-4

Cited by 117 publications

(107 citation statements)

References 22 publications

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“…The concentration of hK6 in tumour cell extract was quantified with a highly sensitive and specific non-competitive immunoassay for hK6 that has been previously described and evaluated in detail (Diamandis et al, 2000c). The assay incorporated two hK6-specific polyclonal antibodies, one raised in mouse and the other in rabbit, in a sequential two site immunometric format with time resolved fluorescence detection.…”

Section: Measurement Of Hk6 In Ovarian Cell Extractsmentioning

confidence: 99%

“…hK6 is a trypsin-like serine protease of unknown physiologic function that is secreted as a 223 amino acid protein. hK6 has been found in various biological fluids including milk from lactating women, nipple aspirate fluid, breast cyst fluid, male and female serum, seminal plasma, and amniotic fluid (Diamandis et al, 2000c). Various tissues express the hK6 gene and synthesize the protein (Diamandis et al, 2000c;Yousef et al, 1999).…”

mentioning

confidence: 99%

“…hK6 has been found in various biological fluids including milk from lactating women, nipple aspirate fluid, breast cyst fluid, male and female serum, seminal plasma, and amniotic fluid (Diamandis et al, 2000c). Various tissues express the hK6 gene and synthesize the protein (Diamandis et al, 2000c;Yousef et al, 1999). Expression is particularly prominent in the brain (Yamashiro et al, 1997), and this, along with the amyloidogenic potential of hK6 (Little et al, 1997) has raised the possibility of a role for hK6 in amyloid precursor processing and the development of Alzheimer's disease.…”

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confidence: 99%

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Immunofluorometric quantitation and histochemical localisation of kallikrein 6 protein in ovarian cancer tissue: a new independent unfavourable prognostic biomarker

et al. 2002

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Human kallikrein 6 protein is a newly discovered human kallikrein. We determined the amount of human kallikrein 6 in extracts of 182 ovarian tumours and correlated specific activity (ng hK6 mg 71 total protein) with clinicopathological variables documented at the time of surgical excision and with outcome (progression free survival, overall survival) monitored over a median interval of 62 months. Thirty per cent of the tumours were positive for human kallikrein 6 (435 ng hK6 mg 71 total protein). Human kallikrein 6-specific immunohistochemical staining of four ovarian tissues that included benign, borderline and malignant lesions indicated a cytoplasmic location of human kallikrein 6 in tumour cells of epithelial origin, although the intensity of staining was variable. Tumour human kallikrein 6 (ng hK6 mg 71 total protein) was higher in late stage disease, serous histotype, residual tumour 41 cm and suboptimal debulking (41 cm) (P50.05). Univariate analysis revealed that patients with tumour human kallikrein 6 positive specific activity were more likely to suffer progressive disease and to die (hazard ratio 1.71 (P=0.015) and 1.88 (P=0.022), respectively). Survival curves demonstrated the same (P=0.013 and 0.019, respectively). Multivariate analysis revealed that human kallikrein 6 positivity was retained as an independent prognostic variable in several subgroups of patients, namely those with (low) grade I and II tumours (hazard ratio progression free survival 4.3 (P=0.027) and overall survival 4.1 (P=0.023)) and those with optimal debulking (hazard ratio progression free survival 3.8 (P=0.019) and overall survival 5.6 (P=0.011)). We conclude that tumour kallikrein 6 protein levels have utility as an independent adverse prognostic marker in a subgroup of ovarian cancer patients with otherwise apparently good prognosis.

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Section: Measurement Of Hk6 In Ovarian Cell Extractsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Immunofluorometric quantitation and histochemical localisation of kallikrein 6 protein in ovarian cancer tissue: a new independent unfavourable prognostic biomarker

et al. 2002

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“…Breast cyst fluids were analyzed with two highly sensitive and specific immunofluorometric assays for PEPC and PGDS, described in detail elsewhere (18,21). Both assays utilize monoclonal capture and detection antibodies, and are used in a one-step procedure.…”

Section: Pepc and Pgds Determinationsmentioning

confidence: 99%

“…It has been previously documented that women with gross cystic breast disease accumulate PEPC in their cyst fluid (17). We have recently developed an immunofluorometric assay for PEPC in order to determine its distribution in various body fluids (18).…”

Section: Introductionmentioning

confidence: 99%

Quantification of pepsinogen C and prostaglandin D synthase in breast cyst fluid and their potential utility for cyst type classification

Borchert

Melegos

et al. 1999

Clinical Biochemistry

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Biochemical pathways mediated by KLK6 protease in breast cancer

et al. 2019

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Kallikrein‐related peptidase 6 (KLK6) is a serine protease normally expressed in mammary tissue and aberrantly regulated in breast cancer. At physiological levels, KLK6 functions as a suppressor of breast cancer, while its aberrant overexpression (> 50‐fold higher than normal) is characteristic of a subset of breast cancers and has been linked to accelerated growth of primary breast tumors in severe combined immunodeficiency mice (Pampalakis et al. Cancer Res 2009, 69, 3779). Here, we investigated the molecular mechanisms underlying the concentration‐dependent functions of KLK6 by comparing MDA‐MB‐231 stable transfectants expressing increasing levels of KLK6 in in vitro and in vivo tumorigenicity assays (soft agar, xenograft growth, tail vein metastasis). Quantitative proteomics was applied to identify proteins that are altered upon re‐expression of KLK6 in MDA‐MB‐231 at normal or constitutive levels. Overexpression of KLK6 is associated with increased metastatic ability of breast cancer cells into lungs, increased expression of certain S100 proteins (S100A4, S100A11) and keratins (KRT), and downregulation of the apoptosis‐related proteases CASP7 and CASP8, and RABs. On the other hand, KLK6 re‐expression at physiological levels leads to inhibition of lung metastases associated with suppression of S100 proteins (S100A4, S100A10, S100A13, S100A16) and induced CASP7 and CASP8 expression. As this is the first report that KLK6 expression is associated with S100 proteins, caspases, RABs, and KRTs, we validated this finding in clinical datasets. By integrating proteomics and microarray data from breast cancer patients, we generated two composite scores, KLK6 + S100B‐S100A7 and KLK6 + S100B‐S100A14‐S100A16, to predict long‐term survival of breast cancer patients. We present previously unknown pathways implicating KLK6 in breast cancer. The findings promise to aid our understanding of the functional roles of KLK6 in breast cancer and may yield new biomarkers for the cancer types in which KLK6 is known to be aberrantly upregulated.

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Immunofluorometric assay of human kallikrein 6 (zyme/protease M/neurosin) and preliminary clinical applications

Cited by 117 publications

References 22 publications

Immunofluorometric quantitation and histochemical localisation of kallikrein 6 protein in ovarian cancer tissue: a new independent unfavourable prognostic biomarker

Immunofluorometric quantitation and histochemical localisation of kallikrein 6 protein in ovarian cancer tissue: a new independent unfavourable prognostic biomarker

Quantification of pepsinogen C and prostaglandin D synthase in breast cyst fluid and their potential utility for cyst type classification

Biochemical pathways mediated by KLK6 protease in breast cancer

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