A Hematogenous Route for Medulloblastoma Leptomeningeal Metastases

被引：82

作者：

Garzia, Livia ^{[1
,2
]}

Kijima, Noriyuki ^{[1
,2
]}

Morrissy, A. Sorana ^{[1
,2
]}

De Antonellis, Pasqualino ^{[1
,2
]}

Guerreiro-Stucklin, Ana ^{[1
,2
]}

Holgado, Borja L. ^{[1
,2
]}

Wu, Xiaochong ^{[1
,2
]}

Wang, Xin ^{[1
,2
,3
]}

Parsons, Michael ^{[4
]}

Zayne, Kory ^{[1
,2
]}

Manno, Alex ^{[1
,2
]}

Kuzan-Fischer, Claudia ^{[1
,2
]}

Nor, Carolina ^{[1
,2
]}

Donovan, Laura K. ^{[1
,2
]}

Liu, Jessica ^{[1
,2
]}

Qin, Lei ^{[1
,2
]}

Garancher, Alexandra ^{[5
]}

Liu, Kun-Wei ^{[5
]}

Mansouri, Sheila ^{[6
]}

Luu, Betty ^{[1
,2
]}

Thompson, Yuan Yao ^{[1
,2
,3
]}

Ramaswamy, Vijay ^{[2
,7
]}

Peacock, John ^{[1
,2
]}

Farooq, Hamza ^{[1
,2
,3
]}

Skowron, Patryk ^{[1
,2
,3
]}

Shih, David J. H. ^{[1
,2
,3
]}

Li, Angela ^{[8
]}

Ensan, Sherine ^{[8
]}

Robbins, Clinton S. ^{[8
,9
]}

Cybulsky, Myron ^{[3
,10
]}

Mitra, Siddhartha ^{[11
]}

Ma, Yussanne ^{[12
,13
]}

Moore, Richard ^{[12
,13
]}

Mungall, Andy ^{[12
,13
]}

Cho, Yoon-Jae ^{[14
,15
,16
]}

Weiss, William A. ^{[17
]}

Chan, Jennifer A. ^{[18
]}

Hawkins, Cynthia E. ^{[2
,18
]}

Massimino, Maura ^{[19
]}

Jabado, Nada ^{[20
]}

Zapotocky, Michal ^{[7
,21
]}

Sumerauer, David ^{[21
]}

Bouffet, Eric ^{[2
,7
]}

Dirks, Peter ^{[2
,26
]}

Tabori, Uri ^{[2
]}

Sorensen, Poul H. B. ^{[22
]}

Brastianos, Priscilla K. ^{[23
]}

Aldape, Kenneth ^{[6
]}

Jones, Steven J. M. ^{[12
,13
]}

Marra, Marco A. ^{[12
,13
]}

机构：

[1] Hosp Sick Children, Dev & Stem Cell Biol Program, Toronto, ON, Canada

[2] Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON, Canada

[3] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada

[4] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada

[5] Sanford Burnham Prebys Med Discovery Inst, NCI Designated Canc Ctr, Tumor Initiat & Maintenance Program, La Jolla, CA USA

[6] Univ Hlth Network, Princess Margaret Canc Ctr, MacFeeters Hamilton Brain Tumour Ctr, Toronto, ON, Canada

[7] Hosp Sick Children, Div Haematol Oncol, Toronto, ON, Canada

[8] Univ Toronto, Dept Immunol, Toronto, ON, Canada

[9] Univ Hlth Network, Toronto Gen Res Inst, Peter Munk Cardiac Ctr, Toronto, ON, Canada

[10] Univ Hlth Network, Toronto Gen Res Inst, Toronto, ON, Canada

[11] Stanford Univ, Sch Med, Dept Neurosurg, Stanford, CA USA

[12] Univ British Columbia, BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC, Canada

[13] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada

[14] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA

[15] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA

[16] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA

[17] Univ Calgary, Dept Pathol & Lab Med, Calgary, AB, Canada

[18] Hosp Sick Children, Div Pathol, Toronto, ON, Canada

[19] Fdn IRCCS Ist Nazl Tumori, Milan, Italy

[20] McGill Univ, Div Hematol Oncol, Montreal, PQ, Canada

[21] Charles Univ Prague, Univ Hosp Moto, Fac Med 2, Dept Pediat Hematol & Oncol, Prague, Czech Republic

[22] British Columbia Canc Res Ctr, Dept Mol Oncol, Vancouver, BC, Canada

[23] Massachusetts Gen Hosp, Div Neurooncol, Boston, MA 02114 USA

[24] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA

[25] Univ Utah, Huntsman Canc Inst, Dept Neurosurg, Salt Lake City, UT USA

[26] Hosp Sick Children, Div Neurosurg, Toronto, ON, Canada

来源：

CELL | 2018年 / 172卷 / 05期

基金：

加拿大健康研究院;

关键词：

NERVOUS-SYSTEM; LEUKEMIA; MICE; COMPLICATIONS; RECURRENCE; EXPRESSION; SUBGROUPS; PATHWAY; CCR2;

D O I：

10.1016/j.cell.2018.01.038

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

While the preponderance of morbidity and mortality in medulloblastoma patients are due to metastatic disease, most research focuses on the primary tumor due to a dearth of metastatic tissue samples and model systems. Medulloblastoma metastases are found almost exclusively on the leptomeningeal surface of the brain and spinal cord; dissemination is therefore thought to occur through shedding of primary tumor cells into the cerebrospinal fluid followed by distal re-implantation on the leptomeninges. We present evidence for medulloblastoma circulating tumor cells (CTCs) in therapy-naive patients and demonstrate in vivo, through flank xenografting and parabiosis, that medulloblastoma CTCs can spread through the blood to the leptomeningeal space to form leptomeningeal metastases. Medulloblastoma leptomeningeal metastases express high levels of the chemokine CCL2, and expression of CCL2 in medulloblastoma in vivo is sufficient to drive leptomeningeal dissemination. Hematogenous dissemination of medulloblastoma offers a new opportunity to diagnose and treat lethal disseminated medulloblastoma.

引用

页码：1050 / +

页数：27

共 23 条

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