Differential Expression of the CCN Family Member WISP-1, WISP-2 and WISP-3 in Human Colorectal Cancer and the Prognostic Implications

Int J Oncol. 2010 May;36(5):1129-36. doi: 10.3892/ijo_00000595.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CCN Intercellular Signaling Proteins
  • Cell Differentiation
  • Cell Line, Tumor
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / metabolism*
  • DNA Primers / genetics
  • DNA, Complementary / metabolism
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry / methods
  • Insulin-Like Growth Factor Binding Proteins / biosynthesis*
  • Intercellular Signaling Peptides and Proteins / biosynthesis*
  • Intracellular Signaling Peptides and Proteins
  • Models, Biological
  • Prognosis
  • Proto-Oncogene Proteins / biosynthesis*
  • Repressor Proteins
  • Transcription Factors / biosynthesis*

Substances

  • CCN Intercellular Signaling Proteins
  • CCN4 protein, human
  • CCN5 protein, human
  • CCN6 protein, human
  • DNA Primers
  • DNA, Complementary
  • Insulin-Like Growth Factor Binding Proteins
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Transcription Factors