2012年8月22日 訊 /生物谷BIOON/ --黑色素瘤的危險(xiǎn)在于它們?cè)诜浅Ｔ缙诘碾A段促進(jìn)新的淋巴管產(chǎn)生，并且因此能夠很早地產(chǎn)生轉(zhuǎn)移性腫瘤,。故此,，找到抑制淋巴管生成(lymphangiogenesis)的蛋白是至關(guān)重要的。在這項(xiàng)研究中,，來自?shī)W地利維也納醫(yī)科大學(xué)皮膚科的Heide Niederleithner和同事們?nèi)缃褡C實(shí)就惡性黑色素瘤而言,，Wnt1是一種能夠抑制淋巴管生成和轉(zhuǎn)移性腫瘤形成的蛋白,。
臨床前研究表明增加信號(hào)蛋白Wnt1釋放抑制新的淋巴途徑形成,，因此也就抑制轉(zhuǎn)移性腫瘤的產(chǎn)生。在此之前,，Wnt1的這種效應(yīng)是未知的,，但是如今維也納醫(yī)科大學(xué)研究人員發(fā)現(xiàn)這種效應(yīng)，并對(duì)此申請(qǐng)專利,。Heide Niederleithner說,，“當(dāng)前，人們還沒有能夠影響淋巴管生成的治療性概念,。發(fā)現(xiàn)Wnt1的這種新的抗淋巴管生成功能代表著在未來人們能夠利用它來治療患有處于某個(gè)階段的黑色素瘤的病人方面取得的一次重要進(jìn)步,。”
論文通信作者Peter Petzelbauer說，這項(xiàng)研究結(jié)果為在這個(gè)領(lǐng)域進(jìn)一步開展研究提供一個(gè)起點(diǎn),，“目前已有其他的研究正在開展以便找到選擇性比Wnt1更好的物質(zhì)和更加詳細(xì)地研究它的信號(hào)途徑,。”(生物谷Bioon.com)
本文編譯自New discoveries in skin cancer: protein inhibits formation of metastases
doi: 10.1038/jid.2012.138
PMC:
PMID:
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.
