Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages.
S1P has been proposed to contribute to cancer progression by regulating tumor proliferation, invasion, and angiogenesis. We developed a biospecific monoclonal antibody to S1P to investigate its role in tumorigenesis. The anti-S1P mAb substantially reduced tumor progression and in some cases eliminated measurable tumors in murine xenograft and allograft models. Tumor growth inhibition was attributed to antiangiogenic and antitumorigenic effects of the antibody. The anti-S1P mAb blocked EC migration and resulting capillary formation, inhibited blood vessel formation induced by VEGF and bFGF, and arrested tumor-associated angiogenesis. The anti-S1P mAb also neutralized S1P-induced proliferation, release of proangiogenic cytokines, and the ability of S1P to protect tumor cells from apoptosis in several tumor cell lines, validating S1P as a target for therapy.
Visentin
Barbara
B
Department of Biology, San Diego State University, San Diego, California 92182, USA.
Vekich
John A
JA
Sibbald
Bradley J
BJ
Cavalli
Amy L
AL
Moreno
Kelli M
KM
Matteo
Rosalia G
RG
Garland
William A
WA
Lu
Yiling
Y
Yu
Shuangxing
S
Hall
Hassan S
HS
Kundra
Vikas
V
Mills
Gordon B
GB
Sabbadini
Roger A
RA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000918:Antibody Specificity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008246:Lysophospholipids / Q000276:immunology*; D051379:Mice; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000276:immunology
D000911:Antibodies, Monoclonal; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine