Nature：舊理論點亮癌癥治療新思路
英國倫敦大學解剖與發育生物學和倫敦皇家學院細胞與分子生物學系的研究人員從細胞接觸性排斥現象中獲得啟發，
找到一種新的癌癥治療思路，相關文章發表在Nature出版前的12月10日的網上在線版上。
50年前，Abercrombie發現在體外培養成纖維細胞的時候，當成纖維細胞相互接觸后會產生接觸性抑制移行（contact inhibition of locomotion）現象，當一個成纖維細胞接觸到另一個細胞的時候會改變移動的方向，掉頭向另一個方向移動。這一現象被認為是生物體內的一個防止細胞惡性侵襲的機制。然而，接觸性抑制移行現象的分子機制一直未被科學家破解。
并且，科學家們現在還沒在活體中發現這一現象的存在。在本研究中，研究小組以神經管嵴細胞（neural crest cells）為研究對象，神經管嵴細胞是一類具有高度移動性和干細胞多能性的細胞群，因此，它的移行可以與惡性細胞侵入相比，是研究接觸性抑制移行（活體內或體外）的最佳模型。
當兩個神經管嵴細胞相遇，它們會收回移動的觸角，改變移動方向，互不侵犯。然而，當一個神經管嵴細胞遇到另一類細胞時，它不會產生抑制接觸現象，而是侵入到另一種組織中。這一模式與癌細胞轉移相似，癌癥轉移灶中的癌細胞也具有相似的能力。
研究小組發現，抑制非經典的Wnt信號（non-canonical Wnt signalling）可同時抑制接觸性抑制移行和神經管嵴細胞的定向移動能力。Wnt信號局限在細胞接觸的位點，誘導該區域RhoA激活。
這些研究成果首次在活體中展現了細胞接觸性抑制移行現象，了解非經典Wnt信號對接觸性抑制移行的影響。
研究者認為，癌癥細胞就是缺乏接觸性移行抑制能力，才導致過渡地擴散到其它健康的組織中，因此，這一發現為癌癥治療提供了新思路，非經典Wnt信號通路是治療癌癥的新靶位。
原文檢索：Contact inhibition of locomotion in vivo controls neural crest directional migration
【Abstract】
Contact inhibition of locomotion was discovered by Abercrombie more than 50 years ago and describes the behaviour of fibroblast cells confronting each other in vitro, where they retract their protrusions and change direction on contact1, 2. Its failure was suggested to contribute to malignant invasion3, 4, 5, 6. However, the molecular basis of contact inhibition of locomotion and whether it also occurs in vivo are still unknown. Here we show that neural crest cells, a highly migratory and multipotent embryonic cell population, whose behaviour has been likened to malignant invasion6, 7, 8, demonstrate contact inhibition of locomotion both in vivo and in vitro, and that this accounts for their directional migration. When two migrating neural crest cells meet, they stop, collapse their protrusions and change direction. In contrast, when a neural crest cell meets another cell type, it fails to display contact inhibition of locomotion; instead, it invades the other tissue, in the same manner as metastatic cancer cells3, 5, 9. We show that inhibition of non-canonical Wnt signalling abolishes both contact inhibition of locomotion and the directionality of neural crest migration. Wnt-signalling members localize at the site of cell contact, leading to activation of RhoA in this region. These results provide the first example of contact inhibition of locomotion in vivo, provide an explanation for coherent directional migration of groups of cells and establish a previously unknown role for non-canonical Wnt signalling.
