Angiotropism, Pericytic Mimicry and Extravascular Migratory Metastasis in Melanoma: An Alternative to Intravascular Cancer Dissemination

Cancer Microenvironment - Tập 7 - Trang 139-152 - 2014
Claire Lugassy1, Sohila Zadran2,3, Laurent A. Bentolila4, Madhuri Wadehra1, Roshini Prakash5, S. Thomas Carmichael5, Hynda K. Kleinman6, Bruno Péault7,8, Lionel Larue9,10,11, Raymond L. Barnhill1,12
1Department of Pathology and Laboratory Medicine and Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at University of California Los Angeles UCLA, Los Angeles, USA
2Department of Neurology, University of California, San Francisco (UCSF), San Francisco, USA
3California Institute of Quantitative Biosciences, San Francisco, USA
4Advanced Light Microscopy/Spectroscopy Lab, California NanoSystems Institute and Department ofChemistry and Biochemistry, University of California Los Angeles (UCLA), Los Angeles, USA
5Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, USA
6National Institutes of Health, Bethesda, USA
7Orthopedic Hospital Research Center and Broad Stem Cell Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, USA
8MRC Center for Regenerative Medicine and BHF Center for Cardiovascular Science, Queens Medical Research Institute University of Edinburgh, Edinburgh, UK
9Institut Curie, Normal and Pathological Development of Melanocytes, Orsay, France
10CNRS UMR3347, Orsay, France
11INSERM U1021, Orsay, France
12Department of Pathology, Institut Curie, Los Paris, France

Tóm tắt

Trong hơn 15 năm qua, hiện tượng angiotropism ở u hắc tố đã được nhấn mạnh như một dấu hiệu của sự di cư ngoài mạch của tế bào khối u dọc theo bề mặt mạch máu ngoại vi, mở ra một cơ chế thay thế cho sự lan rộng của khối u khác với sự phát tán trong lòng mạch. Cơ chế này đã được gọi là sự di căn ngoài mạch (EVMM). Trong quá trình EVMM, các tế bào khối u angiotropic di chuyển theo cách giống như ‘pericytic’ (giả lập pericytic) dọc theo các bề mặt bên ngoài của các kênh mạch, mà không xâm nhập vào lòng mạch. Thông qua con đường này, các tế bào u hắc tố có thể lan rộng đến các vị trí lân cận hoặc xa hơn. Angiotropism là một yếu tố dự đoán nguy cơ di căn trong u hắc tố ở người và là một dấu hiệu của EVMM trong một số mô hình thí nghiệm. Quan trọng là, sự tương đồng giữa EVMM và sự giả lập pericytic bao gồm sự di cư của tế bào đỉnh thần kinh, sự hình thành mạch và sự hình thành mạch máu, và các nghiên cứu gần đây đã gợi ý rằng sự tương tác giữa các tế bào u hắc tố và bề mặt mạch máu ngoại vi gây ra sự biểu hiện khác nhau của các gen gợi nhớ đến sự di cư của khối u và quá trình chuyển tiếp trạng thái tế bào phôi/ tế bào gốc. Một nghiên cứu gần đây đã tiết lộ rằng việc tiếp xúc với tia UV lặp đi lặp lại ở các khối u hắc tố da nguyên phát trong một mô hình chuột được chỉnh sửa gen thúc đẩy sự tiến triển di căn thông qua angiotropism và di cư dọc theo bề mặt mạch máu ngoại vi. Cuối cùng, dữ liệu gần đây sử dụng hình ảnh các tế bào u hắc tố trong một mô hình chuột đã cho thấy sự tiến triển của các tế bào khối u dọc theo các bề mặt mạch máu. Khi xem xét tổng thể, các dữ liệu này hỗ trợ cho hiện tượng sinh học của angiotropism và EVMM, điều này có thể mở ra những chiến lược mới đầy hứa hẹn để giảm thiểu hoặc ngăn ngừa sự di căn của u hắc tố.

Từ khóa

#angiotropism #di căn ngoài mạch #u hắc tố #pericytic mimicry #di cư tế bào #di căn.

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