Critical role of the NOTCH ligand JAG2 in self-renewal of myeloma cells

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• 作者：David Chiron^a ; ^b ; ¹ ; Sophie Maï ; ga^a ; ^b ; ² ; Gé ; raldine Descamps^a ; ^b ; ² ; Philippe Moreau^c ; ³ ; Steven Le Gouill^a ; ^c ; ³ ; Sé ; verine Marionneau^d ; ⁴ ; Thibauld Ouiller^d ; ⁴ ; Jé ; rô ; me Moreaux^e ; ⁵ ; Bernard Klein^e ; ⁵ ; Ré ; gis Bataille^a ; ^b ; ^f ; ⁶ ; Martine Amiot^a ; ^b ; ⁶ ; Catherine Pellat-Deceunynck^a ; ^b ; ⁷ ; ^{catherine.pellat-deceunynck@inserm.fr}
• 刊名：Blood Cells ; Molecules ; and Diseases
• 出版年：2012
• 期刊代码：277_10799796
• 类别：med
• 出版时间：15 April, 2012
• 卷：48
• 期：4
• 页码：247-253
• 文件大小：788 K

摘要

The purpose of this study was to identify the pathways associated with the ability of CD138⁺ human myeloma cells to form colonies in a serum-free semi-solid human collagen-based assay. Only 26%(7 of 27) of human myeloma cell lines were able to spontaneously form colonies. This spontaneous clonogenic growth correlated with the expression of the NOTCH ligand JAG2 (p < 0.001). Blocking JAG-NOTCH interactions with NOTCH-Fc chimeric molecules impaired self-colony formation, indicating a role for JAG-NOTCH pathway in colony formation. In two cell lines, silencing of JAG2 blocked both colony formation and in vivo tumor formation in immunocompromised mice. RT-PCR and flow cytometry analysis revealed that JAG2 is often expressed by CD138⁺ primary cells. Our results indicate that spontaneous clonogenic growth of myeloma cells requires the expression of JAG2.