2012年8月22日 讯 /生物谷BIOON/ --黑色素瘤的危险在于它们在非常早期的阶段促进新的淋巴管产生，并且因此能够很早地产生转移性肿瘤。故此，找到抑制淋巴管生成(lymphangiogenesis)的蛋白是至关重要的。在这项研究中，来自奥地利维也纳医科大学皮肤科的Heide Niederleithner和同事们如今证实就恶性黑色素瘤而言，Wnt1是一种能够抑制淋巴管生成和转移性肿瘤形成的蛋白。
临床前研究表明增加信号蛋白Wnt1释放抑制新的淋巴途径形成，因此也就抑制转移性肿瘤的产生。在此之前，Wnt1的这种效应是未知的，但是如今维也纳医科大学研究人员发现这种效应，并对此申请专利。Heide Niederleithner说，“当前，人们还没有能够影响淋巴管生成的治疗性概念。发现Wnt1的这种新的抗淋巴管生成功能代表着在未来人们能够利用它来治疗患有处于某个阶段的黑色素瘤的病人方面取得的一次重要进步。”
论文通信作者Peter Petzelbauer说，这项研究结果为在这个领域进一步开展研究提供一个起点，“目前已有其他的研究正在开展以便找到选择性比Wnt1更好的物质和更加详细地研究它的信号途径。”(生物谷Bioon.com)
本文编译自New discoveries in skin cancer: protein inhibits formation of metastases
doi: 10.1038/jid.2012.138
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Wnt1 Is Anti-Lymphangiogenic in a Melanoma Mouse Model
Heide Niederleithner, Magdalena Heinz, Stefanie Tauber, Martin Bilban, Hubert Pehamberger, Stefan Sonderegger, Martin Knöfler, Andreas Bracher, Walter Berger, Robert Loewe and Peter Petzelbauer
Wnt signals contribute to melanoma progression by boosting their proliferation and survival. Initially, we expected that activated Wnt signaling also improves their proficiency to recruit blood and lymph vessels. To assess this, we added cell culture supernatants (SNs) of Wnt1+ and Wnt1− melanoma to endothelial spheroids. Whereas SNs of Wnt1− melanoma cells induced lymphatic sprouts, those of Wnt1+ cells were unable to do so and this was restored by vascular endothelial growth factor C (VEGF-C). Subsequent testing of several human melanoma lines revealed that Wnt1 suppressed their VEGF-C expression. This Wnt1 effect did not depend on glycogen synthase kinase-3β (GSK3β), β-catenin, or activator protein-1, but was blocked by cyclosporine A (CsA). To analyze Wnt1 effects in melanoma in vivo, we selected Wnt1− melanoma cell lines, overexpressed Wnt1, and injected them subepidermally into severe combined immunodeficient (SCID) mice. We found reduced VEGF-C expression, reduced lymphangiogenesis, and delayed metastasis to sentinel nodes in Wnt1+ as compared with Wnt1− melanoma (P<0.05). Concomitant overexpression of VEGF-C or feeding of animals with CsA restored lymphangiogenesis and metastasis in Wnt1+ melanoma. In conclusion, Wnt1 is anti-lymphangiogenic by suppressing melanoma-derived VEGF-C expression.
