Proteasome inhibitor bortezomib targeted tumor-endothelial cell interaction in T-cell leukemia/lymphoma.
Endothelial cells have special relevance in tumor progression. Here, we investigated the effect of the proteasome inhibitor bortezomib on tumor-endothelial cell interaction in T-cell leukemia/lymphoma. In vitro, T-leukemia/lymphoma cell lines and primary T-leukemia/lymphoma cells were cultured with endothelial cells, either together or separately in Millicell Hanging Cell Culture system, the latter permits mutual cell exchange. At clinically achievable concentrations, in addition to a direct cytotoxicity on T-leukemia/lymphoma cells, bortezomib inhibited tumor cell adhesion to endothelial cells and endothelial cell migration toward tumor cells. In vivo, a murine tumor xenograft model was achieved by subcutaneous injection of Jurkat cells. Bortezomib also triggered an inhibition on tumor-endothelial cell contact and subsequent tumor cell infiltration. Cell adhesion molecule intracellular cell adhesion molecule-1 expression was significantly downregulated both on the tumor cells and on the endothelial cells. Taken together, bortezomib could not only act on tumor cells themselves but also abrogate tumor cell interaction with endothelial cells. This delineates another therapeutic mechanism of bortezomib in T-cell malignancies.
Shi
Wen-Yu
WY
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, Shanghai 200025, China.
Wang
Li
L
Xiao
Dan
D
Yao
Yin
Y
Yang
Fan
F
Jiang
Xiao-Xing
XX
Leboeuf
Christophe
C
Janin
Anne
A
Chen
Sai-Juan
SJ
Zhao
Wei-Li
WL
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D002450:Cell Communication / Q000187:drug effects* / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008819:Mice, Nude; D058990:Molecular Targeted Therapy / Q000379:methods*; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D001897:Boronic Acids; D004791:Enzyme Inhibitors; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib