Scientific Reports (Aug 2017)

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

  • Peng-Peng Xu,
  • Yi-Feng Sun,
  • Ying Fang,
  • Qi Song,
  • Zi-Xun Yan,
  • Yi Chen,
  • Xu-Feng Jiang,
  • Xiao-Chun Fei,
  • Yan Zhao,
  • Christophe Leboeuf,
  • Biao Li,
  • Chao-Fu Wang,
  • Anne Janin,
  • Li Wang,
  • Wei-Li Zhao

DOI
https://doi.org/10.1038/s41598-017-07964-5
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 10

Abstract

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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-β (TGF-β)/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-β/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.