Differential expression and prognostic implications of the CCN family members WISP-1, WISP-2, and WISP-3 in human breast cancer.
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.
Davies
Simon R
SR
Metastasis and Angiogenesis Research Group, Department of Surgery, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN, United Kingdom. Simondavies@doctors.org.uk
Watkins
Gareth
G
Mansel
Robert E
RE
Jiang
Wen G
WG
D042501:Angiogenic Proteins / Q000032:analysis; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D055511:CCN Intercellular Signaling Proteins; D045744:Cell Line, Tumor; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000032:analysis*; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis*; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis*; D008207:Lymphatic Metastasis / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins; D014157:Transcription Factors / Q000032:analysis*; D025521:Tumor Suppressor Proteins / Q000032:analysis
D042501:Angiogenic Proteins; D055511:CCN Intercellular Signaling Proteins; C116396:CCN4 protein, human; C413323:CCN5 protein, human; C400081:CCN6 protein, human; D018969:Insulin-Like Growth Factor Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins