PH Regulation by Breast Cancer Cells in Vitro and in Vivo.
Abstract
The pH of tumors plays an important role in therapeutic efficacy, and may have relevance to carcinogenesis itself. A technique has been developed to simultaneously measure the extracellular pH (pHe) and the intracellular pH (pHi) of tumors in vivo using in vivo Magnetic Resonance Spectroscopy (MRS). During the past year, this technique has been refined to accurately report the pHe distribution within the tumor. This is significant since at the low extremes therapy using weakly basic chemotherapeutic agents, such as doxorubicin, is significantly hindered. A quantitative model has demonstrated that the turnover of acidic vesicles within cells can also contribute to cellular resistance to weakly basic chemotherapeutic drugs. During the past year, this model has been developed and measurements of acidic vesicle turnover have begun. Drug resistant MCF/7 cell variants have a higher rate of vesicle turnover rate than do their drug-sensitive counterparts. Furthermore, they express a plasma membrane activity of vacuolar-type H(+) ATPases (V-ATPases) which may be a consequence of this vesicle turnover. In order to quantify the turnover of these V-ATPase containing vesicles, antibodies against an extracellular epitope of the pump are required.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1996
- Accession Number
- ADA320398
Entities
People
- Robert J Gillies
Organizations
- University of Arizona