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研究分野生物医学と臨床科学医学微生物学医学菌学
研究分野
生物医学と臨床科学
医学微生物学
医学菌学
メドゥロブラストーマ・レプトメニンゲル転移の血液経路

メドゥロブラストーマ・レプトメニンゲル転移の血液経路

Livia Garzia ¹, Noriyuki Kijima ¹, A Sorana Morrissy ¹, Pasqualino De Antonellis ¹, Ana Guerreiro-Stucklin ¹, Borja L Holgado ¹, Xiaochong Wu ¹, Xin Wang ², Michael Parsons ³, Kory Zayne ¹, Alex Manno ¹, Claudia Kuzan-Fischer ¹, Carolina Nor ¹, Laura K Donovan ¹, Jessica Liu ¹, Lei Qin ¹, Alexandra Garancher ⁴, Kun-Wei Liu ⁴, Sheila Mansouri ⁵, Betty Luu ¹, Yuan Yao Thompson ², Vijay Ramaswamy ⁶, John Peacock ¹, Hamza Farooq ², Patryk Skowron ², David J H Shih ², Angela Li ⁷, Sherine Ensan ⁷, Clinton S Robbins ⁸, Myron Cybulsky ⁹, Siddhartha Mitra ¹⁰, Yussanne Ma ¹¹, Richard Moore ¹¹, Andy Mungall ¹¹, Yoon-Jae Cho ¹², William A Weiss ¹³, Jennifer A Chan ¹⁴, Cynthia E Hawkins ¹⁵, Maura Massimino ¹⁶, Nada Jabado ¹⁷, Michal Zapotocky ¹⁸, David Sumerauer ¹⁹, Eric Bouffet ⁶, Peter Dirks ²⁰, Uri Tabori ²¹, Poul H B Sorensen ²², Priscilla K Brastianos ²³, Kenneth Aldape ⁵, Steven J M Jones ¹¹, Marco A Marra ¹¹, James R Woodgett ³, Robert J Wechsler-Reya ²⁴, Daniel W Fults ²⁵, Michael D Taylor ²⁶

Livia Garzia ¹, Noriyuki Kijima ¹, A Sorana Morrissy ¹

¹Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
²Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
³Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
⁴Tumor Initiation and Maintenance Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
⁵MacFeeters-Hamilton Brain Tumour Centre, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
⁶The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada.
⁷Department of Immunology, University of Toronto, Toronto, ON, Canada.
⁸Department of Immunology, University of Toronto, Toronto, ON, Canada; Peter Munk Cardiac Centre, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.
⁹Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Toronto General Research Institute, University Health Network, Toronto, ON, Canada.
¹⁰Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
¹¹Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency and Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
¹²Departments of Pediatrics, Neurological Surgery and Neurology, University of California, San Francisco, San Francisco, CA, USA.
¹³Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada.
¹⁴Division of Pathology, The Hospital for Sick Children, Toronto, ON, Canada.
¹⁵The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Division of Pathology, The Hospital for Sick Children, Toronto, ON, Canada.
¹⁶Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
¹⁷Division of Hematology/Oncology, McGill University, Montreal, QC, Canada.
¹⁸Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, University Hospital Motol, Charles University, Prague, Czech Republic.
¹⁹Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, University Hospital Motol, Charles University, Prague, Czech Republic.
²⁰The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada.
²¹The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
²²Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada.
²³Division of Neuro-Oncology, Massachusetts General Hospital, Boston, MA, USA.
²⁴Tumor Initiation and Maintenance Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA; Department of Pediatrics, University of California, San Diego, San Diego, CA, USA.
²⁵Department of Neurosurgery, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
²⁶Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada.

⁰Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.

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2018年2月24日

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2018年2月24日

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PubMedで要約を見る

まとめ

この要約は機械生成です。

骨髄芽細胞の癌細胞は血流を移動して広がり,レプトメニゲル転移を形成します. ケモカインCCL2をターゲットにすることで,髄芽細胞腫の拡散を診断し,治療する新しい方法が提供される可能性があります.

科学分野

腫瘍学
神経科学
癌の転移に関する研究

背景

骨髄芽細胞腫の死亡率は主に転移性疾患によるものですが,転移性サンプルが不足しているため研究が制限されています.
髄芽細胞腫の転移は主にレプトメニンゲアル表面に発生し,脳脊髄液の拡散を示唆する.
現在,髄芽細胞腫の広がりに関する理解は不完全であり,効果的な治療戦略を阻害しています.

研究の目的

循環中の腫瘍細胞 (CTC) の存在と役割を調査する.
骨髄芽細胞のCTCが血流経由で広がり,レプトメニンゲル転移を形成するかどうかを判断する.
レプトメニンゲアル伝播を誘発する分子機構を特定し,特にCCL2の役割を明らかにする.

主な方法

治療前の患者で循環する腫瘍細胞 (CTC) の検出
横の異種移植とパラバイオスを用いて,血性拡散をモデル化したイン・ビボ試験.
メドゥロブラストーマのレプトメニンゲアル転移におけるケモカインCCL2発現の分析

主要な成果

治療前の患者における髄芽細胞腫CTCの証拠
髄芽細胞腫のCTCが血液中に広がり,体内ではレプトメニンゲル転移を形成する.
レプトメニンゲル転移でCCL2の高い発現で,CCL2が拡散を誘導するのに十分である.

結論

髄膜芽細胞は,循環する腫瘍細胞を通して血球的に拡散することができます.
レプトメニンゲル転移はCCL2発現によって引き起こされる.
血液による拡散は,髄芽細胞腫の新たな診断および治療目標を提供します.

キーワード:

脳腫瘍循環する腫瘍細胞骨髄芽細胞腫転移する小児がん

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