The balance between extracellular cathepsins and cystatin C is of importance for ovarian cancer.
BACKGROUND
A major step in cancer formation involves the degradation of the extracellular matrix, mediated by multiple degradative actions of (lysosomal) proteases. Extracellular release of lysosomal proteases (cathepsins) and their inhibitors has been associated with the development and progression of several types of cancer. We investigated whether cathepsins in ovarian cyst fluid (oCF) were associated with disease outcome in patients with epithelial ovarian cancer (EOC).


METHODS
The levels of cathepsin B (CatB), H (CatH), L (CatL) and X (CatX) and their most abundant extracellular inhibitor cystatin C (CysC) were determined in oCF of 50 EOC patients by quantitative ELISAs. The cathepsin levels and ratios between cathepsins and CysC were related to clinicopathological parameters (Mann-Whitney U and Kruskal-Wallis tests) and survival (Cox Regression analysis).


RESULTS
Median (25th-75th percentile) levels of cathepsin B, H, L, X and CysC in oCF were 97 (42-203), 18 (12-32), 61 (37-108), 20 (13-47) and 657 (501-805) ng mL(-1) respectively. Ratio of CysC/CatB was significantly lower for patients with metastatic compared with localised EOC (P = 0.025). Ratios of CysC/CatH and CysC/CatX differed significantly between histological subtypes (P = 0.012 and P = 0.035 respectively) and were significantly higher for high-grade tumours compared with low-grade tumours (P = 0.031 and P = 0.039 respectively). Neither cathepsins nor their ratios were significant predictors of survival for EOC patients.


CONCLUSIONS
Ratios between CysC and cathepsins in oCF differed significantly between important clinicopathological subgroups. We believe that a complex cascade of proteolytic events, in which cathepsins play different roles, might be responsible for progression and metastasis in EOC.
Kolwijck
Eva
E
Department of Obstetrics and Gynecology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. e.kolwijck@obgyn.umcn.nl
Kos
Janko
J
Obermajer
Natasja
N
Span
Paul N
PN
Thomas
Chris M G
CM
Massuger
Leon F A G
LF
Sweep
Fred C G J
FC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002403:Cathepsins / Q000032:analysis / Q000378:metabolism*; D020420:Cyst Fluid / Q000737:chemistry / Q000378:metabolism*; D055316:Cystatin C / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010048:Ovarian Cysts / Q000737:chemistry / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D011379:Prognosis
D014408:Biomarkers, Tumor; D055316:Cystatin C; D002403:Cathepsins