- Title
-
JAM-A overexpression is related to disease progression in diffuse large B-cell lymphoma and downregulated by lenalidomide
- Authors
- Xu, P.P., Sun, Y.F., Fang, Y., Song, Q., Yan, Z.X., Chen, Y., Jiang, X.F., Fei, X.C., Zhao, Y., Leboeuf, C., Li, B., Wang, C.F., Janin, A., Wang, L., Zhao, W.L.
- Source
- Full text @ Sci. Rep.
JAM-A indicated B-lymphoma cell stemness. (A) As assessed by Whole-mount in Situ Hybridization and real-time quantitative RT-PCR, c-myb and runx1 were overexpressed after 26 h microinjecting jam-1 mRNA (jam-1) in Zebrafish embryos. WT, wild type. (B,C) B-lymphoma cell line DB and SU-DHL-4 were transfected with control vector (Vector) and JAM-A vector (JAM-A). Ectopic expression of JAM-A was associated with increased colony formation (B) and stem-cell marker CD133 and CD34 expression (C). (D) DLBCL patients with high JAM-A expression displayed increased CD133 positivity. (E) Patients in high JAM-A expression group were enriched for a stem cell gene signature, as revealed by RNA sequencing. Data in (A), (B) and (C) are representative of three independent experiments. EXPRESSION / LABELING:
|
JAM-A activated TGF-β/NODAL signaling. (A,B) In JAM-A-transfected DB cells (A) and DLBCL patients (B), JAM-A overexpression was related to activation of TGF-β/NODAL signaling. (C) As assessed by Whole-mount in Situ Hybridization and real-time quantitative RT-PCR, ndr-1 and ndr-2 were increased in jam-1-overexpressing zebrafish. WT, wild type. (D) JAM-A upregulated NODAL expression, which was restored by specific TGF-β/NODAL/Smad inhibitor SB431542 or JAM-A ShRNA. SB431542 abrogated JAM-A-induced lymphoma cell invasion (E) JAM-A was the highest in patients with involvement of endoderm-derived organs, followed by those with involvement of mesoderm- and ectoderm-derived organs. (F) JAM-A correlated with increased NODAL expression in primary lymph nodes, as well as in secondary lesions. Data in (C) are representative of three independent experiments. |