Different matrix micro-environments in colon cancer and diverticular disease.
OBJECTIVE
The extracellular matrix and the interactive signalling between its components are thought to play a pivotal role for tumour development and metastasis formation. An altered matrix composition as potential underlying pathology for the development of colorectal cancer was hypothesized.


METHODS
In a retrospective study of patients with colon cancer, the extracellular matrix in tumour-free bowel specimen was investigated in comparison with non-infected bowel specimen from patients operated on for colonic diverticulosis. The following matrix parameters with known associations to tumour formation, cell proliferation, invasion and metastasis were analysed by immunohistochemistry and quantified by a scoring system: VEGF, TGF-beta, ESDN, CD117, c-erb-2, cyclin D1, p53, p27, COX-2, YB-1, collagen I/III, MMP-13, PAI and uPAR. Expression profiles and correlations were calculated.


RESULTS
The comparison of the two groups revealed a significantly decreased immunostaining for CD117 and TGF-beta in the cancer group (8.5+/-2.6 vs 10.3+/-2,1 and 4.9+/-1.5 vs 8.1+/-3, respectively), whereas PAI scores were significantly higher than in patients with diverticular disease (8.1+/-1.6 vs 6.2+/-0.9). Overall correlation patterns of matrix parameters indicated pronounced differences between tumour-free tissue in cancer patients compared with patients with diverticular disease.


CONCLUSIONS
Our results indicate distinct differences in the colonic tissue architecture between cancer patients and patients with diverticulitis that support the notion of an altered matrix composition predisposing to the development of colon cancer.
Klinge
U
U
Department of Surgery of the RWTH-Aachen, RWTH-Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany, r.rosch@chir.rwth-aachen.de.
Rosch
R
R
Junge
K
K
Krones
C J
CJ
Stumpf
M
M
Lynen-Jansen
P
P
Mertens
P R
PR
Schumpelick
V
V
D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D003106:Colon / Q000378:metabolism / Q000601:surgery; D012809:Colon, Sigmoid / Q000378:metabolism / Q000601:surgery; D003110:Colonic Neoplasms / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D043963:Diverticulosis, Colonic / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012189:Retrospective Studies; D016212:Transforming Growth Factor beta / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D051840:Y-Box-Binding Protein 1
D024042:Collagen Type I; D024061:Collagen Type III; D019938:Cyclin D1; D051546:Cyclooxygenase 2; D004268:DNA-Binding Proteins; D053509:Matrix Metalloproteinase 13; D008565:Membrane Proteins; D009687:Nuclear Proteins; D017395:Plasminogen Activator Inhibitor 1; D019009:Proto-Oncogene Proteins c-kit; D018719:Erb-b2 Receptor Tyrosine Kinases; D016212:Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D051840:Y-Box-Binding Protein 1; C436326:DCBLD2 protein, human; C467484:VEGFA protein, human; C070856:YBX1 protein, human; C496540:PTGS2 protein, human