Proton pumps, angiogenesis, and metastatic breast cancer

Jose D. Rojas, Shankar C. Sanka, Defeng Luo, Christian Busch, Gloria M. Martinez, Mary J.C. Hendrix, Raul Martinez-Zaguilan

Research output: Contribution to journalConference article

2 Scopus citations

Abstract

We have previously shown the relationship between metastatic potential and plasmalemmal V-H+-ATPase (pm V-ATPase) expression in tumor cells. This led us to hypothesize that pm V-ATPase activity is involved in invasion. Angiogenesis involves invasion of adjacent tissues by microvascular endothelial cells, thus we hypothesized that pm V-ATPases contribute to pHin regulation and invasion in microvascular endothelial cells. Immunocytochemical experiments revealed pm V-ATPases at the leading edge of cancer and microvascular endothelial cells. We monitored pHin from leading- to lagging-edge at the single cell level using confocal/spectral imaging microscopy. Our data indicate that the pHin is more alkaline at the leading than at the lagging edge, in both these cell types, suggesting the presence of pHin gradients. Line scanning confocal microscopy demonstrated pHin oscillations whose magnitude were larger in the lagging than the leading edge. Exposure of the cell's leading edge to bafilomycin A1, a V-H+-ATPase inhibitor, decreased the migratory capabilities of the cells. Inhibitors for P- and F-type ATPases had no effect on these phenomena. Altogether, these data indicate that pm V-ATPases play a role in pHin regulation and invasion in tumor and microvascular endothelial cells. This could offer a potential target to modulate angiogenesis and metastasis.

Original languageEnglish (US)
Pages (from-to)67-78
Number of pages12
JournalProceedings of SPIE - The International Society for Optical Engineering
Volume3924
StatePublished - Jan 1 2000
Externally publishedYes
EventMolecular Imaging: Reporters, Dyes, Markers, and Instrumentation - San Jose, CA, USA
Duration: Jan 23 2000Jan 24 2000

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Condensed Matter Physics
  • Computer Science Applications
  • Applied Mathematics
  • Electrical and Electronic Engineering

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  • Cite this

    Rojas, J. D., Sanka, S. C., Luo, D., Busch, C., Martinez, G. M., Hendrix, M. J. C., & Martinez-Zaguilan, R. (2000). Proton pumps, angiogenesis, and metastatic breast cancer. Proceedings of SPIE - The International Society for Optical Engineering, 3924, 67-78.