Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages

Barbara Visentin; John A. Vekich; Bradley J. Sibbald; Amy L. Cavalli; Kelli M. Moreno; Rosalia G. Matteo; William A. Garland; Yiling Lu; Shuangxing Yu; Hassan S. Hall; Vikas Kundra; Gordon B. Mills; Roger A. Sabbadini

doi:10.1016/j.ccr.2006.02.023

Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages

Barbara Visentin, John A. Vekich, Bradley J. Sibbald, Amy L. Cavalli, Kelli M. Moreno, Rosalia G. Matteo, William A. Garland, Yiling Lu, Shuangxing Yu, Hassan S. Hall, Vikas Kundra, Gordon B. Mills, Roger A. Sabbadini

Research output: Contribution to journal › Article › peer-review

405 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	225-238
Number of pages	14
Journal	Cancer Cell
Volume	9
Issue number	3
DOIs	https://doi.org/10.1016/j.ccr.2006.02.023
State	Published - Mar 2006
Externally published	Yes

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

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10.1016/j.ccr.2006.02.023

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Visentin, B., Vekich, J. A., Sibbald, B. J., Cavalli, A. L., Moreno, K. M., Matteo, R. G., Garland, W. A., Lu, Y., Yu, S., Hall, H. S., Kundra, V., Mills, G. B., & Sabbadini, R. A. (2006). Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages. Cancer Cell, 9(3), 225-238. https://doi.org/10.1016/j.ccr.2006.02.023

Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages. / Visentin, Barbara; Vekich, John A.; Sibbald, Bradley J.; Cavalli, Amy L.; Moreno, Kelli M.; Matteo, Rosalia G.; Garland, William A.; Lu, Yiling; Yu, Shuangxing; Hall, Hassan S.; Kundra, Vikas; Mills, Gordon B.; Sabbadini, Roger A.

In: Cancer Cell, Vol. 9, No. 3, 03.2006, p. 225-238.

Research output: Contribution to journal › Article › peer-review

Visentin, B, Vekich, JA, Sibbald, BJ, Cavalli, AL, Moreno, KM, Matteo, RG, Garland, WA, Lu, Y, Yu, S, Hall, HS, Kundra, V, Mills, GB & Sabbadini, RA 2006, 'Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages', Cancer Cell, vol. 9, no. 3, pp. 225-238. https://doi.org/10.1016/j.ccr.2006.02.023

Visentin, Barbara ; Vekich, John A. ; Sibbald, Bradley J. ; Cavalli, Amy L. ; Moreno, Kelli M. ; Matteo, Rosalia G. ; Garland, William A. ; Lu, Yiling ; Yu, Shuangxing ; Hall, Hassan S. ; Kundra, Vikas ; Mills, Gordon B. ; Sabbadini, Roger A. / Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages. In: Cancer Cell. 2006 ; Vol. 9, No. 3. pp. 225-238.

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title = "Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages",

abstract = "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.",

author = "Barbara Visentin and Vekich, {John A.} and Sibbald, {Bradley J.} and Cavalli, {Amy L.} and Moreno, {Kelli M.} and Matteo, {Rosalia G.} and Garland, {William A.} and Yiling Lu and Shuangxing Yu and Hall, {Hassan S.} and Vikas Kundra and Mills, {Gordon B.} and Sabbadini, {Roger A.}",

note = "Funding Information: This work was supported by NIH R43 CA110298-01 (A.L.C, R.A.S.); PO1 CA64602 and DAMD 17-02-1-0694 (G.B.M.); an International Research Doctorate on Molecular and Cellular Pharmacology (B.V.); and Lpath, Inc. R.A.S., A.L.C., W.A.G., B.J.S, B.V., K.M.M., J.A.V., and G.B.M. have stock options in Lpath, Inc. ",

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AU - Cavalli, Amy L.

AU - Moreno, Kelli M.

AU - Matteo, Rosalia G.

AU - Garland, William A.

AU - Lu, Yiling

AU - Yu, Shuangxing

AU - Hall, Hassan S.

AU - Kundra, Vikas

AU - Mills, Gordon B.

AU - Sabbadini, Roger A.

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N2 - 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.

AB - 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.

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Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages

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