In Vivo Expansion of Cancer Stemness Affords Novel Cancer Stem Cell Targets: Malignant Rhabdoid Tumor as an Example

被引：28

作者：

Golan, Hana ^{[1
,2
,3
,7
,12
]}

Shukrun, Rachel ^{[1
,2
,3
,12
]}

Caspi, Revital ^{[1
,2
,3
,12
]}

Vax, Einav ^{[1
,2
,3
,12
]}

Pode-Shakked, Naomi ^{[1
,2
,3
,4
,12
]}

Goldberg, Sanja ^{[1
]}

Pleniceanu, Oren ^{[1
,2
,3
,12
]}

Bar-Lev, Dekel D. ^{[1
]}

Mark-Danieli, Michal ^{[1
,2
,3
]}

Pri-Chen, Sara ^{[5
]}

Jacob-Hirsch, Jasmine ^{[2
,3
]}

Kanter, Itamar ^{[9
,10
]}

Trink, Ariel ^{[9
,10
]}

Schiby, Ginette ^{[8
,12
]}

Bilik, Ron ^{[11
]}

Kalisky, Tomer

Harari-Steinberg, Orit ^{[1
,2
,3
,12
]}

Toren, Amos ^{[1
,2
,3
,7
,12
]}

Dekel, Benjamin ^{[1
,2
,3
,6
,12
]}

机构：

[1] Edmond & Lily Sara Childrens Hosp, Sheba Med Ctr, Pediat Stem Cell Res Inst, IL-52621 Ramat Gan, Israel

[2] Sheba Med Ctr, Sheba Ctr Regenerat Med, IL-52621 Ramat Gan, Israel

[3] Sheba Med Ctr, Sheba Canc Res, IL-52621 Ramat Gan, Israel

[4] Sheba Med Ctr, Dr Pinchas Borenstein Talpiot Med Leadership Prog, IL-52621 Ramat Gan, Israel

[5] Sheba Med Ctr, Maurice & Gabriela Goldschleger Eye Res Inst, IL-52621 Ramat Gan, Israel

[6] Safra Childrens Hosp, Sheba Med Ctr, Div Pediat Nephrol, IL-52621 Ramat Gan, Israel

[7] Edmond & Lily Safra Childrens Hosp, Sheba Med Ctr, Div Pediat Hematooncol, IL-52621 Ramat Gan, Israel

[8] Sheba Med Ctr, Dept Pathol, IL-52621 Ramat Gan, Israel

[9] Bar Ilan Univ, Fac Engn, IL-5290002 Ramat Gan, Israel

[10] Bar Ilan Univ, Nanotechnol Inst, IL-5290002 Ramat Gan, Israel

[11] Edmond & Lily Safra Childrens Hosp, Sheba Med Ctr, Dept Pediat Surg, IL-52621 Ramat Gan, Israel

[12] Tel Aviv Univ, Sackler Sch Med, IL-6997801 Tel Aviv, Israel

来源：

STEM CELL REPORTS | 2018年 / 11卷 / 03期

关键词：

LYSYL OXIDASE LOX; CHROMATIN SUPRAORGANIZATION; MESENCHYMAL TRANSITION; WILMS-TUMOR; EXPRESSION; XENOGRAFTS; TRANSCRIPTION; POPULATIONS; MARKER; KIDNEY;

D O I：

10.1016/j.stemcr.2018.07.010

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Cancer stem cell (CSC) identification relies on transplantation assays of cell subpopulations sorted from fresh tumor samples. Here, we attempt to bypass limitations of abundant tumor source and predetermined immune selection by in vivo propagating patient-derived xenografts (PDX) from human malignant rhabdoid tumor (MRT), a rare and lethal pediatric neoplasm, to an advanced state in which most cells behave as CSCs. Stemness is then probed by comparative transcriptomics of serial PDXs generating a gene signature of epithelial to mesenchymal transition, invasion/motility, metastasis, and self-renewal, pinpointing putative MRT CSC markers. The relevance of these putative CSC molecules is analyzed by sorting tumorigenic fractions from early-passaged PDX according to one such molecule, deciphering expression in archived primary tumors, and testing the effects of CSC molecule inhibition on MRT growth. Using this platform, we identify ALDH1 and lysyl oxidase (LOX) as relevant targets and provide a larger framework for target and drug discovery in rare pediatric cancers.

引用

页码：795 / 810

页数：16

共 41 条

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