Differential expression of the CCN family member WISP-1, WISP-2 and WISP-3 in human colorectal cancer and the prognostic implications.
The WISPs (Wnt-inducted secreted proteins, WISP-1, WISP-2 and WISP-3) are part of the CCN family. These molecules are known to play a diverse role in cells but their role in cancer cells remains controversial. We analysed the expression of the three WISP molecules at the mRNA and protein levels in a cohort of 94 human colorectal tumours and 80 normal colorectal tissues and correlated the results with the pathological features and clinical outcome of the patients. WISP-1 transcripts were found at higher levels in the tumour samples than in the normal tissue (p=0.0015); higher in patients with Dukes stage B and C compared to Dukes A (p=0.017 and p=0.024, respectively); higher in patients with moderately and poorly differentiated cancers compared to the well differentiated cancers (p=0.020 and p=0.076, respectively and p=0.0035 when combined); higher in node positive tumours compared with the node negative (p=0.11) and in the patients with higher TNM staging (TNM 2, 3 and 4 compared to TNM 1 p=0.037). WISP-2 showed the opposite pattern with lower levels of expression in cancer cells compared to normal (p=0.082). Although no significant differences were found within the cancer group when indices of a more aggressive tumour were compared to the normal tissue a significant reduction in expression was found (Dukes C p=0.044, poorly differentiated p=0.019, TNM 3 p=0.020 and node positive disease p=0.048). WISP-3 transcript levels showed no significant differences between groups. WISPs may play important but contrasting roles in colorectal cancer with WISP-1 appearing to act as a factor stimulating aggressiveness, WISP-2 as a tumour suppressor and WISP-3 having no definable beneficial or detrimental role.
Davies
Simon R
SR
Metastasis and Angiogenesis Research Group, Cardiff University School of Medicine, Heath Park, CF14 4XN Cardiff, UK.
Davies
Mansel Leigh
ML
Sanders
Andrew
A
Parr
Chris
C
Torkington
Jared
J
Jiang
Wen G
WG
D055511:CCN Intercellular Signaling Proteins; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D018969:Insulin-Like Growth Factor Binding Proteins / Q000096:biosynthesis*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D047908:Intracellular Signaling Peptides and Proteins; D008954:Models, Biological; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D012097:Repressor Proteins; D014157:Transcription Factors / Q000096:biosynthesis*
D055511:CCN Intercellular Signaling Proteins; C116396:CCN4 protein, human; C413323:CCN5 protein, human; C400081:CCN6 protein, human; D017931:DNA Primers; D018076:DNA, Complementary; D018969:Insulin-Like Growth Factor Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D014157:Transcription Factors