Davies Simon R, Watkins Gareth, Mansel Robert E, Jiang Wen G
Metastasis and Angiogenesis Research Group, Department of Surgery, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN, United Kingdom.
Ann Surg Oncol. 2007 Jun;14(6):1909-18. doi: 10.1245/s10434-007-9376-x. Epub 2007 Apr 4.
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.
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.
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.
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.
CCN家族有三种由Wnt诱导的分泌蛋白，即WISP-1、WISP-2和WISP-3。已知这些分子在细胞中发挥多种作用，但其在癌细胞中的作用仍存在争议。
在本研究中，我们分析了122例人类乳腺肿瘤和32例正常乳腺组织中三种WISP分子在mRNA和蛋白质水平的表达情况，并将这些结果与患者的临床结局相关联。
与无淋巴结转移的肿瘤相比，有淋巴结转移的肿瘤中WISP-1转录本水平较低（P <.05）；与预后良好组相比，中度（P =.01）和诺丁汉预后指数预后较差（P <.05）的患者中WISP-1转录本水平较低；与1级分化肿瘤相比，3级分化肿瘤中WISP-1转录本水平显著较低（P <.05）；发生转移并死于乳腺癌相关原因的患者中WISP-1转录本水平较低（两项比较P均<.05）。WISP-2的情况几乎相反，在有淋巴结转移的肿瘤中表达水平更高（P =.0043）；与预后良好组相比，中度和预后较差组中WISP-2表达水平均较高（均P <.05）；与1级相比，2级和3级中WISP-2表达水平均更高（均P <.05）；发生转移的患者中WISP-2表达水平更高（P <.01）。WISP-3转录本水平在各组之间无统计学显著差异。
WISP在乳腺癌中可能发挥重要但相反的作用。WISP-1似乎起抑癌作用，WISP-2则是刺激肿瘤侵袭性的因素；WISP-3没有明确的有益或有害作用。
