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

Metastasis and Angiogenesis Research Group, Department of Surgery, University Hospital of Wales, Heath Park, Cardiff CF14 4XN, United Kingdom

Correspondence: Address correspondence and reprint requests to: Simon R. Davies, MRCS; E-mail: Simondavies{at}doctors.org.uk

Background: The CCN family has three Wnt-inducted secreted proteins named WISP-1, WISP-2 and WISP-3. These molecules are known to play a diverse role in cells, but their role in cancer cells remains controversial.

Methods: In this study, we analyzed the expression of the three WISP molecules at the mRNA and protein levels in a cohort of 122 human breast tumors and 32 normal breast tissues, and we correlated these findings with patients’ clinical outcomes.

Results: WISP-1 transcripts were found in lower levels in node-positive tumors compared with node-negative tumors (P < .05); were lower in patients with a moderate (P = .01) and poor Nottingham Prognostic Index prognosis (P < .05) compared with good prognostic groups; were of significantly lower level in grade 3 differentiated tumors (P < .05) compared with grade 1; and were of lower levels in patients who developed metastasis and died from breast cancer–related causes (P < .05 in both comparisons). Almost the reverse was found to be true for WISP-2, which had greater levels of expression in node-positive tumors (P = .0043); higher levels in both moderate and poor prognostic groups compared with the good prognostic group (both P < .05); greater level in both grade 2 and 3 when compared with grade 1 (both P < .05); and higher levels in patients who went on to develop metastases (P < .01). WISP-3 transcript levels showed no statistically significant differences between groups.

Conclusions: WISPs may play important but contrasting roles in breast cancer. WISP-1 seems to act as a tumor suppressor and WISP-2 as a factor that stimulates aggressiveness; WISP-3 has no definable beneficial or detrimental role.

Key Words: WISP-1 • WISP-2 • WISP-3 • CCN • Breast cancer

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