Characterizing human colorectal carcinomas by proteolytic profile.
Clinicopathologic staging of colorectal cancers cannot always predict aggressiveness of prognosis for a particular patient. We have used activity assays for cysteine proteinases, cathepsins B, L and H (CB, CL and CH) and matrix metalloproteinases, MMP-2 and MMP-9, to identify several distinctive, reproducible proteolytic profiles in a large set of colorectal carcinomas. We observed that individual proteinases demonstrated specific and distinct levels of activity at different cancer stages, possible reflecting non-random steps in a proteolytic cascade related to tumor development. We also observed that individual colon cancers fell into relatively few categories when characterized for the combined expression of three proteinases: CB, CL and MMP-9. Four proteolytic profiles, designated "Early", "Middle", "Late", and "High", could be used to define almost 80% of the colorectal carcinomas analyzed. Such profiles, based on the expression of several proteinases in a given tumor, provided information independent of clinical stage and may identify crucial variations in tumor behavior.
Murnane
M J
MJ
Department of Pathology, Boston University School of Medicine, MA 02118, USA. mmurnane@acs.bu.edu
Shuja
S
S
Del Re
E
E
Cai
J
J
Iacobuzio-Donahue
C
C
Klepeis
V
V
D014408:Biomarkers, Tumor; D002401:Cathepsin B / Q000378:metabolism; D056655:Cathepsin H; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000175:diagnosis / Q000201:enzymology*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D010450:Endopeptidases; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000378:metabolism; D009367:Neoplasm Staging
D014408:Biomarkers, Tumor; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; C534126:CTSH protein, human; D056655:Cathepsin H; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9