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Angiostatin-like activity of a monoclonal antibody to the catalytic subunit of F1F0 ATP synthase.

Publication ,  Journal Article
Chi, SL; Wahl, ML; Mowery, YM; Shan, S; Mukhopadhyay, S; Hilderbrand, SC; Kenan, DJ; Lipes, BD; Johnson, CE; Marusich, MF; Capaldi, RA ...
Published in: Cancer Res
May 15, 2007

The antiangiogenic protein angiostatin inhibits ATP synthase on the endothelial cell surface, blocking cellular proliferation. To examine the specificity of this interaction, we generated monoclonal antibodies (mAb) directed against ATP synthase. mAb directed against the beta-catalytic subunit of ATP synthase (MAb3D5AB1) inhibits the activity of the F(1) domain of ATP synthase and recognizes the catalytic beta-subunit of ATP synthase. We located the antibody recognition site of MAb3D5AB1 in domains containing the active site of the beta-subunit. MAb3D5AB1 also binds to purified Escherichia coli F(1) with an affinity 25-fold higher than the affinity of angiostatin for this protein. MAb3D5AB1 inhibits the hydrolytic activity of F(1) ATP synthase at lower concentrations than angiostatin. Like angiostatin, MAb3D5AB1 inhibits ATP generation by ATP synthase on the endothelial cell surface in acidic conditions, the typical tumor microenvironment where cell surface ATP synthase exhibits greater activity. MAb3D5AB1 disrupts tube formation and decreases intracellular pH in endothelial cells exposed to low extracellular pH. Neither angiostatin nor MAb3D5AB1 showed an antiangiogenic effect in the corneal neovascularization assay; however, both were effective in the low-pH environment of the chicken chorioallantoic membrane assay. Thus, MAb3D5AB1 shows angiostatin-like properties superior to angiostatin and may be exploited in cancer chemotherapy.

Duke Scholars

Published In

Cancer Res

DOI

ISSN

0008-5472

Publication Date

May 15, 2007

Volume

67

Issue

10

Start / End Page

4716 / 4724

Location

United States

Related Subject Headings

  • Rats, Inbred F344
  • Rats
  • Oncology & Carcinogenesis
  • Neovascularization, Physiologic
  • Models, Molecular
  • Mitochondrial Proton-Translocating ATPases
  • Mice, Inbred BALB C
  • Mice
  • Hydrogen-Ion Concentration
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chi, S. L., Wahl, M. L., Mowery, Y. M., Shan, S., Mukhopadhyay, S., Hilderbrand, S. C., … Pizzo, S. V. (2007). Angiostatin-like activity of a monoclonal antibody to the catalytic subunit of F1F0 ATP synthase. Cancer Res, 67(10), 4716–4724. https://doi.org/10.1158/0008-5472.CAN-06-1094
Chi, Sulene L., Miriam L. Wahl, Yvonne M. Mowery, Siqing Shan, Somnath Mukhopadhyay, Susana C. Hilderbrand, Daniel J. Kenan, et al. “Angiostatin-like activity of a monoclonal antibody to the catalytic subunit of F1F0 ATP synthase.Cancer Res 67, no. 10 (May 15, 2007): 4716–24. https://doi.org/10.1158/0008-5472.CAN-06-1094.
Chi SL, Wahl ML, Mowery YM, Shan S, Mukhopadhyay S, Hilderbrand SC, et al. Angiostatin-like activity of a monoclonal antibody to the catalytic subunit of F1F0 ATP synthase. Cancer Res. 2007 May 15;67(10):4716–24.
Chi, Sulene L., et al. “Angiostatin-like activity of a monoclonal antibody to the catalytic subunit of F1F0 ATP synthase.Cancer Res, vol. 67, no. 10, May 2007, pp. 4716–24. Pubmed, doi:10.1158/0008-5472.CAN-06-1094.
Chi SL, Wahl ML, Mowery YM, Shan S, Mukhopadhyay S, Hilderbrand SC, Kenan DJ, Lipes BD, Johnson CE, Marusich MF, Capaldi RA, Dewhirst MW, Pizzo SV. Angiostatin-like activity of a monoclonal antibody to the catalytic subunit of F1F0 ATP synthase. Cancer Res. 2007 May 15;67(10):4716–4724.

Published In

Cancer Res

DOI

ISSN

0008-5472

Publication Date

May 15, 2007

Volume

67

Issue

10

Start / End Page

4716 / 4724

Location

United States

Related Subject Headings

  • Rats, Inbred F344
  • Rats
  • Oncology & Carcinogenesis
  • Neovascularization, Physiologic
  • Models, Molecular
  • Mitochondrial Proton-Translocating ATPases
  • Mice, Inbred BALB C
  • Mice
  • Hydrogen-Ion Concentration
  • Humans