A Hematogenous Route for Medulloblastoma Leptomeningeal Metastases.

Cell. 2018 Feb 22;172(5):1050-1062.e14

Authors: Garzia L, Kijima N, Morrissy AS, De Antonellis P, Guerreiro-Stucklin A, Holgado BL, Wu X, Wang X, Parsons M, Zayne Ok, Manno A, Kuzan-Fischer C, Nor C, Donovan LK, Liu J, Qin L, Garancher A, Liu KW, Mansouri S, Luu B, Thompson YY, Ramaswamy V, Peacock J, Farooq H, Skowron P, Shih DJH, Li A, Ensan S, Robbins CS, Cybulsky M, Mitra S, Ma Y, Moore R, Mungall A, Cho YJ, Weiss WA, Chan JA, Hawkins CE, Massimino M, Jabado N, Zapotocky M, Sumerauer D, Bouffet E, Dirks P, Tabori U, Sorensen PHB, Brastianos PK, Aldape Ok, Jones SJM, Marra MA, Woodgett JR, Wechsler-Reya RJ, Fults DW, Taylor MD

Summary
Whereas the preponderance of morbidity and mortality in medulloblastoma sufferers are as a result of metastatic illness, most analysis focuses on the first tumor as a result of a dearth of metastatic tissue samples and mannequin techniques. Medulloblastoma metastases are discovered nearly solely on the leptomeningeal floor of the mind and spinal twine; dissemination is subsequently thought to happen by way of shedding of major tumor cells into the cerebrospinal fluid adopted by distal re-implantation on the leptomeninges. We current proof for medulloblastoma circulating tumor cells (CTCs) in therapy-naive sufferers and reveal in vivo, by way of flank xenografting and parabiosis, that medulloblastoma CTCs can unfold by way of the blood to the leptomeningeal area to type leptomeningeal metastases. Medulloblastoma leptomeningeal metastases categorical excessive ranges of the chemokine CCL2, and expression of CCL2 in medulloblastoma in vivo is enough to drive leptomeningeal dissemination. Hematogenous dissemination of medulloblastoma provides a brand new alternative to diagnose and deal with deadly disseminated medulloblastoma.

PMID: 29474906 [PubMed – in process]