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JAM-A overexpression is related to disease progression in diffuse large B-cell lymphoma and downregulated by lenalidomide.


ABSTRACT: Cancer stem cells play an important role on tumor progression. Biomarkers of stem cell property and their relationship to extranodal involvement of malignant lymphocytes are undefined in diffuse large B-cell lymphoma (DLBCL). Here we showed that junctional adhesion molecule-A (JAM-A) was highly expressed in DLBCL patients with multiple extranodal lesions. JAM-A maintained B-lymphoma cell stemness and was associated with cell invasion and epithelial-to-mesenchymal transition both in vitro and in vivo. As mechanism of action, JAM-A overexpression selectively activated transforming growth factor-? (TGF-?)/NODAL signaling, thereby enhanced B-lymphoma cell aggressiveness and induced extranodal involvement to mesoendoderm-derived organs in DLBCL. Lenalidomide downregulated JAM-A and downstream NODAL expression, resulting in inhibition of B-lymphoma cell invasion and epithelial-to-mesenchymal transition. In a murine xenograft model established with subcutaneous injection of JAM-A-overexpressing B-lymphoma cells, lenalidomide retarded tumor growth and prevented cell invasion to mesoendoderm-derived organs, consistent with the downregulation of JAM-A and NODAL expression. Collectively, these findings indicated that JAM-A was related to extranodal involvement in DLBCL through modulating TGF-?/NODAL signaling. Identified as a biomarker of stem cell property, JAM-A indicated the sensitivity of B-lymphoma cells to lenalidomide. Therapeutic targeting of JAM-A/NODAL axis could thus be a promising clinical strategy to impede tumor progression in DLBCL.

SUBMITTER: Xu PP 

PROVIDER: S-EPMC5547054 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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JAM-A overexpression is related to disease progression in diffuse large B-cell lymphoma and downregulated by lenalidomide.

Xu Peng-Peng PP   Sun Yi-Feng YF   Fang Ying Y   Song Qi Q   Yan Zi-Xun ZX   Chen Yi Y   Jiang Xu-Feng XF   Fei Xiao-Chun XC   Zhao Yan Y   Leboeuf Christophe C   Li Biao B   Wang Chao-Fu CF   Janin Anne A   Wang Li L   Zhao Wei-Li WL  

Scientific reports 20170807 1


Cancer stem cells play an important role on tumor progression. Biomarkers of stem cell property and their relationship to extranodal involvement of malignant lymphocytes are undefined in diffuse large B-cell lymphoma (DLBCL). Here we showed that junctional adhesion molecule-A (JAM-A) was highly expressed in DLBCL patients with multiple extranodal lesions. JAM-A maintained B-lymphoma cell stemness and was associated with cell invasion and epithelial-to-mesenchymal transition both in vitro and in  ...[more]

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