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        7. 《自然》子刊:癌細胞形態變化與入侵方式的新發現

          發布時間:2021年11月01日 09:09:25 來源:振東健康網

          《自然》子刊:癌細胞形態變化與入侵方式的新發現

          資訊作者:Weill Cornell Medical College

          編輯翻譯:奇奇

          本文獻于2021年10月27日發表在國際期刊《Scientific Reports》上。俄勒岡州立大學的研究人員們揭示了惡性細胞改變其形狀以及入侵不同類型組織的遷移方式,有助于了解和預防癌癥轉移。

          俄勒岡州立大學的一項研究揭示了惡性細胞改變其形狀以及入侵不同類型組織的遷移方式。

          發表在《科學報告》上的這一發現,是了解和預防癌癥轉移的關鍵一步。癌癥轉移是疾病的內部傳播,是導致95%癌癥死亡的原因。

          領導這項研究的俄亥俄州立大學生物物理學家Bo Sun說:“經過數十億年的進化,細胞已經學會了許多不同的遷移方式。在正常發育和維持健康的生理過程中(如傷口愈合),需要時細胞就會執行特定的遷移程序。然而,在腫瘤的情況下,癌細胞利用這些遷移程序來維持它們對組織的入侵?!?/span>

          圖注:黃色:肌動蛋白。粉色:絲狀偽足。綠色:半球氣泡。藍色:板狀偽足。紅色:小氣泡。


          孫博士解釋說,癌細胞改變形狀和移動模式的能力對癌癥患者的預后起著巨大的作用。

          他說:“許多針對細胞特定移動方式的癌癥療法無法阻止腫瘤轉移,很大程度上是因為細胞轉向了另一個可用的遷移程序?!?/span>

          孫博士和他在俄勒岡州立大學科學與工程學院的合作者使用了一種被稱為計算機視覺的人工智能,這種技術能根據細胞的形狀跟蹤細胞的遷移程序,能讓計算機視覺從數字照片、視頻和其他視覺輸入中來獲取信息。

          在這項研究中,科學家們觀察了MDA-MB-23細胞,這是一種常用于醫學研究的高侵襲性乳腺癌細胞。孫博士說細胞形狀分析就好像根據游泳者的身體姿勢和動作來判斷游泳者的游泳方式一樣。

          孫博士說:“細胞形狀是由細胞功能決定的,特征形狀的喪失與功能異常有關。這就是為什么形狀特征一直是診斷癌癥以及其他疾病(如紅細胞疾病或神經系統疾病)的重要工具?!?他說,研究結果表明,癌細胞改變其遷移模式的頻率遠比之前認為的要高。

          “雖然我們在研究的乳腺癌細胞中看到的不斷轉換并不一定會使它們在特定類型組織中的速度最大化,但它允許細胞入侵異質組織環境?!睂O博士說到。

          研究人員指出,在轉移過程中,遷移的癌細胞必須通過具有不同力學特性的細胞外基質。細胞外基質(ECM)是組織和器官的非細胞部分。由于其生物活性分子的多樣性,它作為一個支架,執行一系列重要的生化和生物力學工作。

          科學家們通過機器學習和可視化技術表明,細胞的形狀變化是由分子控制中心Rho/rock信號調節的,細胞利用Rho/rock信號感知其物理環境并產生運動所需的力。

          通過研究代表兩個機械上不同的細胞外基質層的模型,科學家們發現當細胞接近和穿過這兩層基質的界面時,它們的形狀和運動程序逐漸發生改變。這表明,這些轉變對癌細胞轉移是必不可少的,這需要非均勻ECM的導航。

          孫博士說:“細胞形態變化的方式(形態動力學)是決定其入侵潛力的關鍵因素,據我們所知,此領域還尚未得到研究。癌細胞遷移的形態動力學正在成為檢查細胞內部狀態和微環境的強大工具。未來的研究需要將形態動力學解碼為豐富和易理解的細胞身體語言,并將影響形態動力學作為一種控制細胞行為的手段?!?/span>


          英文原文

          Research Shows Cancer Cells Change Shape and How They Move to Invade Different Types of Tissue

          Oregon State University research has shed new light on the way malignant cells change their shape and migration techniques to invade different types of tissue.

          The findings, published in Scientific Reports, are a key step toward understanding and preventing cancer metastasis, the internal spreading of the disease that's responsible for 95% of all cancer deaths.

          "Through billions of years of evolution, cells have learned a number of distinct ways to migrate," said OSU biophysicist Bo Sun, who led the study. "In normal development and health-maintaining physiological processes such as wound healing, specific migration programs are executed when required. In the case of a tumor, however, those migration programs are leveraged by cancer cells to sustain their invasion into tissue."

          How well a cancer cell can change shape and shift travel modes plays a huge role in a cancer patient's prognosis, Sun explains.

          "Many cancer therapies that target a particular way a cell moves can fail to stop tumor metastasis in large part because cells switch to another available migration program," he said.

          Sun and collaborators in the OSU colleges of Science and Engineering used a type of artificial intelligence known as computer vision to track a cell's migration program based on its shape; computer vision derives information from digital photos, video and other visual inputs.

          For this study, the scientists looked at cells from MDA-MB-23, a line of highly invasive breast cancer cells that's commonly used in medical research. Sun likens the cell shape analysis to determining whether a swimmer is doing the backstroke, breaststroke or butterfly based on the position swimmers put their body in and the movements they execute.

          "Cell shape is determined by cell function, and loss of characteristic shape is associated with functional abnormality," Sun said. "That's why shape characterization has been an important tool for diagnosis in cancer as well as in other conditions such as red blood cell disease or neurological disorders." The findings show that cancer cells change their migration modes far more often than had been previously thought, he says.

          "While the constant switching we saw in the breast cancer cells we studied doesn't necessarily maximize their speed in a particular type of tissue, it allows for the cells to invade heterogeneous tissue environments," Sun said.

          During metastasis, a migrating cancer cell has to make its way through extracellular matrix that has distinct and varying mechanical properties, the researchers note. The extracellular matrix, or ECM, is the non-cellular part of tissues and organs. It acts as a scaffold and, thanks to its variety of biologically active molecules, performs a range of important biochemical and biomechanical jobs.

          The machine learning and visualization techniques the scientists employed showed that a cell's shape changes are regulated by the molecular control hub, Rho/ROCK-signaling, that a cell uses to sense its physical environment and generate the force required for motion.

          Using a model representing two mechanically distinct layers of extracellular matrix, the scientists showed the cells gradually changed their shape and movement program as they approached and crossed the interface of the layers. That suggests these transitions are essential for cancer cell metastasis, which requires the navigation of non-uniform ECM.

          "The way a cell's form changes—its morphodynamics—is a crucial factor in determining its invasive potential and to our knowledge this has largely gone unstudied," Sun said. "The morphodynamics of migrating cancer cells are shaping up to be a powerful tool for inspecting the internal state and microenvironment of the cells. Future research is needed to decode the morphodynamics into a rich and understandable body language of cells, and to affect morphodynamics as a means of controlling what the cells are doing."


          參考文獻

          Christopher Z. Eddy et al, Morphodynamicsfacilitate cancer cells to navigate 3D extracellular matrix, Scientific Reports(2021).


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