期刊
JOURNAL OF CELLULAR PHYSIOLOGY
卷 226, 期 2, 页码 299-308出版社
WILEY
DOI: 10.1002/jcp.22400
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资金
- Ligue Nationale Contre le Cancer (Equipe labellisee)
- Association pour la Recherche contre le Cancer (ARC)
- Institut National du Cancer (INCa)
- National Agency for Research (ANR)
- Centre A. Lacassagne
- Centre National de la Recherche Scientifique (CNRS)
- Ministere de l'Education, de la Recherche et de la Technologie
- University of Nice
- Natural Sciences and Engineering Research Council of Canada (NSERC PDF)
- EU
- European FP7 program METOXIA
A distinguishing phenotype of solid tumors is the presence of an alkaline cellular feature despite the surrounding acidic microenvironment. This phenotypic characteristic of tumors, originally described by Otto Warburg, arises due to alterations in metabolism of solid tumors. Hypoxic regions of solid tumors develop due to poor vascularization and in turn regulate the expression of numerous genes via the transcription factor HI-I. Ultimately, the tumor microenvironment directs the development of tumor cells adapted to survive in an acidic surrounding where normal cells perish. The provision of unique pH characteristics in tumor cells provides a defining trait that has led to the pursuit of treatments that target metabolism, hypoxia, and pH-related mechanisms to selectively kill cancer cells. Numerous studies over the past decade involving the cancer-specific carbonic anhydrase IX have re-kindled an interest in pH disruption-based therapies. Although an acidification of the intracellular compartment is established as a means to induce normal cell death, the defining role of acid base disturbances in tumor physiology and survival remains unclear. The aim of this review is to summarize recent data relating to the specific role of pH regulation in tumor cell survival. We focus on membrane transport and enzyme studies in an attempt to elucidate their respective functions regarding tumor cell pH regulation. These data are discussed in the context of future directions for the field of tumor cell acid base-related research. J. Cell. Physiol. J. Cell. Physiol. 226: 299-308, 2011. (C) 2010 Wiley-Liss, Inc.
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