Cysteine and serine proteases in gastric cancer.
BACKGROUND
Cysteine proteases (cathepsin B [CATB] and cathepsin L [CATL]), the serine protease urokinase-type plasminogen activator (UPA), and plasminogen activator inhibitor type-1 (PAI-1) are thought to play an important part in cancer invasion and metastasis. The aims of this study were to measure CATB, CATL, UPA, and PAI-1 in gastric cancer (GC) and normal mucosa distant from the tumor (NORM); to evaluate whether tissue levels are related to tumor stage, grade, or histotype; to assess their prognostic relevance; and to examine UPA and PAI-1 expression immunohistochemically.


METHODS
Gastric cancer and NORM samples were obtained from 25 patients with gastric cancer patients undergoing surgery (17 males, 8 females; mean age, 62 years; range, 31-84 years). Antigen concentrations were measured using the enzyme-linked immunosorbent assay method. Immunohistochemistry was performed using monoclonal UPA and PAI-1 antibodies.


RESULTS
Significantly higher antigen levels were found: (1) in GC vs. NORM (CATB, CATL, UPA, PAI-1) tissues; (2) in GC with versus without metastasis (CATB, CATL, UPA); (3) in poorly or moderately versus well differentiated GC; and (4) in diffuse versus intestinal-type GC (CATB, CATL). Urokinase-type plasminogen activator, PAI-1 and CATB levels had a significant prognostic impact. Cancer and stromal cells, showed immunoreactivity to anti-UPA and anti-PAI-1 antibodies.


CONCLUSIONS
These results confirm the important role of CATB, CATL, UPA and PAI-1 in gastric cancer progression. Higher levels are detected in GC with metastases, poorer differentiation, and diffuse histotype, thus identifying patients with a worse prognosis.
Plebani
M
M
Dipartimento di Medicina di Laboratorio, Laboratorio Centrale, Padova, Italy.
Herszènyi
L
L
Cardin
R
R
Roveroni
G
G
Carraro
P
P
Paoli
M D
MD
Rugge
M
M
Grigioni
W F
WF
Nitti
D
D
Naccarato
R
R
D000230:Adenocarcinoma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002401:Cathepsin B / Q000032:analysis; D056668:Cathepsin L; D002403:Cathepsins / Q000032:analysis; D003546:Cysteine Endopeptidases / Q000032:analysis*; D010450:Endopeptidases; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005753:Gastric Mucosa / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D011379:Prognosis; D012697:Serine Endopeptidases / Q000032:analysis*; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis
D017395:Plasminogen Activator Inhibitor 1; D002403:Cathepsins; D010450:Endopeptidases; D012697:Serine Endopeptidases; D014568:Urokinase-Type Plasminogen Activator; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L