Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Hoelzer D, Gokbuget N, Ottmann O, Pui CH, Relling MV, Appelbaum FR, van Dongen JJ, Szczepanski T (2002) Acute lymphoblastic leukemia. Hematology (Am Soc Hematol Educ Program ) 2002:162–192
Savage KJ (2005) Aggressive peripheral t-cell lymphomas (specified and unspecified types). Hematology (Am Soc Hematol Educ Program) 2005:267–277
Mai W, Meng H, Jin J, Wang L (2006) Treatment with bortezomib in a patient with heavily pretreated refractory T-cell lymphoblastic lymphoma. Eur J Haematol 77:445–447
Bonvini P, Zorzi E, Basso G, Rosolen A (2007) Bortezomib-mediated 26S proteasome inhibition causes cell-cycle arrest and induces apoptosis in cd-30+ anaplastic large cell lymphoma. Leukemia 21:838–842
Lee J, Suh C, Kang HJ, Ryoo BY, Huh J, Ko YH, Eom HS, Kim K, Park K, Kim WS (2008) Phase I study of proteasome inhibitor bortezomib plus chop in patients with advanced, aggressive T-cell or NK/T-cell lymphoma. Ann Oncol 19:2079–2083
Zinzani PL, Musuraca G, Tani M, Stefoni V, Marchi E, Fina M, Pellegrini C, Alinari L, Derenzini E, de Vivo A, Sabattini E, Pileri S, Baccarani M (2007) Phase II trial of proteasome inhibitor bortezomib in patients with relapsed or refractory cutaneous T-cell lymphoma. J Clin Oncol 25:4293–4297
Sunwoo JB, Chen Z, Dong G, Yeh N, Crowl Bancroft C, Sausville E, Adams J, Elliott P, Van Waes C (2001) Novel proteasome inhibitor PS-341 inhibits activation of nuclear factor-kappa B, cell survival, tumor growth, and angiogenesis in squamous cell carcinoma. Clin Cancer Res 7:1419–1428
Zhao WL, Liu YY, Zhang QL, Wang L, Leboeuf C, Zhang YW, Ma J, Garcia JF, Song YP, Li JM, Shen ZX, Chen Z, Janin A, Chen SJ (2008) PRDM1 is involved in chemoresistance of T-cell lymphoma and down-regulated by the proteasome inhibitor. Blood 111:3867–3871
Zhang QL, Wang L, Zhang YW, Jiang XX, Yang F, Wu WL, Janin A, Chen Z, Shen ZX, Chen SJ, Zhao WL (2009) The proteasome inhibitor bortezomib interacts synergistically with the histone deacetylase inhibitor suberoylanilide hydroxamic acid to induce T-leukemia/lymphoma cells apoptosis. Leukemia 23:1507–1514
Semenza GL (2003) Angiogenesis in ischemic and neoplastic disorders. Annu Rev Med 54:17–28
Hideshima T, Chauhan D, Schlossman R, Richardson P, Anderson KC (2001) The role of tumor necrosis factor alpha in the pathophysiology of human multiple myeloma: therapeutic applications. Oncogene 20:4519–4527
Kanwar JR, Berg RW, Yang Y, Kanwar RK, Ching LM, Sun X, Krissansen GW (2003) Requirements for ICAM-1 immunogene therapy of lymphoma. Cancer Gene Ther 10:468–476
Belanger SD, St-Pierre Y (2005) Role of selectins in the triggering, growth, and dissemination of T-lymphoma cells: Implication of L-selectin in the growth of thymic lymphoma. Blood 105:4800–4806
Clark PR, Manes TD, Pober JS, Kluger MS (2007) Increased ICAM-1 expression causes endothelial cell leakiness, cytoskeletal reorganization and junctional alterations. J Invest Dermatol 127:762–774
Palombella VJ, Conner EM, Fuseler JW, Destree A, Davis JM, Laroux FS, Wolf RE, Huang J, Brand S, Elliott PJ, Lazarus D, McCormack T, Parent L, Stein R, Adams J, Grisham MB (1998) Role of the proteasome and NF-kappaB in streptococcal cell wall-induced polyarthritis. Proc Natl Acad Sci USA 95:15671–15676
Ahn KS, Sethi G, Chao TH, Neuteboom ST, Chaturvedi MM, Palladino MA, Younes A, Aggarwal BB (2007) Salinosporamide A (NPI-0052) potentiates apoptosis, suppresses osteoclastogenesis, and inhibits invasion through down-modulation of NF-kappaB regulated gene products. Blood 110:2286–2295
Noborio-Hatano K, Kikuchi J, Takatoku M, Shimizu R, Wada T, Ueda M, Nobuyoshi M, Oh I, Sato K, Suzuki T, Ozaki K, Mori M, Nagai T, Muroi K, Kano Y, Furukawa Y, Ozawa K (2009) Bortezomib overcomes cell-adhesion-mediated drug resistance through downregulation of VLA-4 expression in multiple myeloma. Oncogene 28:231–242
McConkey DJ, Zhu K (2008) Mechanisms of proteasome inhibitor action and resistance in cancer. Drug Resist Updat 11:164–179
Hideshima T, Chauhan D, Shima Y, Raje N, Davies FE, Tai YT, Treon SP, Lin B, Schlossman RL, Richardson P, Muller G, Stirling DI, Anderson KC (2000) Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy. Blood 96:2943–2950
Acknowledgments
This work was supported, in part, by the Chinese National High Tech Program (863:2006AA02A301 and 863:2006AA02A405), the National Natural Science Foundation of China (30750335), the Shanghai Commission of Science and Technology (08410708800), the Shanghai Rising Star Program (09QH1401700), the Program for New Century Excellent Talents in University, the Fok Ying Tung Education Foundation (111035), “Shu Guang” project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation, and by the Samuel Waxman Cancer Research Foundation Laboratory, the Co-PI Program of Shanghai Rui Jin Hospital/Shanghai Jiao Tong University School of Medicine.
Author information
Authors and Affiliations
Corresponding author
Additional information
Wen-Yu Shi, Li Wang, Dan Xiao, and Yin Yao contributed equally to this manuscript.
Rights and permissions
About this article
Cite this article
Shi, WY., Wang, L., Xiao, D. et al. Proteasome inhibitor bortezomib targeted tumor–endothelial cell interaction in T-cell leukemia/lymphoma. Ann Hematol 90, 53–58 (2011). https://doi.org/10.1007/s00277-010-1022-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00277-010-1022-1