Proton ATPase are involved in metastasis in human breast cancer cell

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Title: Proton ATPase are involved in metastasis in human breast cancer cell
Author: Luo, Defeng
Abstract: Cancer cells live in a more acidic environment than the normal tissue , but the intracellular pH (pHin ) of tumors is more alkaline than in non -tumor cells . This indicates that cancer cells maintain a larger transmembrane pH gradient than normal cells . Our previous studies suggested that vacuolar type H'*^ -ATPases (V -H'*'ATPases ) that normally reside in acidic organelles may be also expressed at the plasma membrane (pmVATPase ) of highly metastatic human tumors . We hypothesize that pmV -ATPase plays a role in maintaining an alkaline intracellular environment favorable for growth , while maintaining an acidic extracellular environment favorable for invasion . Human breast cancer cell lines with distinct metastatic potential (MCF -7 , MB -231 , MB468 and MB - 435s ) were used as experimental models . Immunocytochemical experiments showed that pmV -ATPases are located at the leading edge of metastatic human breast cancer cells . We employed spectral imaging and line scanning confocal microscopy (LSCM ) to monitor the pHfn of discrete cellular regions , as well as fluorescence spectroscopy to determine proton fluxes in these cancer cell lines . These approaches are complementary in that they offer unsurpassed spatial , temporal and spectral resolution . Our data show that the pHin is more alkaline at the leading than at the lagging edge in the more invasive cells . The magnitude ofthe pHin gradient is larger in the highly than in the lowly metastatic cells . The proton fluxes are faster in the highly than in the lowly metastatic cells . Pharmacological and ion substitution experiments indicated that pmV -H"^ATPase expression was more elevated in the highly than in lowly metastatic cells . Invasion assays of these cancer cells lines show that bafilomycin Ai inhibits the invasive behavior . These novel observations suggest that the magnitude ofthe pH gradients is determined by pmVH^ ATPase , and pmV -H^ ATPase is involved in the invasion ofthe cancer cells .
URI: http : / /hdl .handle .net /2346 /10193
Date: 2001-12

Citation

Luo, Defeng Proton ATPase are involved in metastasis in human breast cancer cell. Master's thesis, Texas Tech University. Available electronically from http : / /hdl .handle .net /2346 /10193 .

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