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Alternating pH landscapes shape epithelial cancer initiation and progression: Focus on pancreatic cancer
Author(s) -
Pedersen Stine F.,
Novak Ivana,
Alves Frauke,
Schwab Albrecht,
Pardo Luis A.
Publication year - 2017
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.201600253
Subject(s) - pancreatic cancer , intracellular ph , tumor microenvironment , stromal cell , extracellular , cancer cell , biology , cancer , microbiology and biotechnology , intracellular , chemistry , biochemistry , cancer research , tumor cells , genetics
We present here the hypothesis that the unique microenvironmental pH landscape of acid‐base transporting epithelia is an important factor in development of epithelial cancers, by rendering the epithelial and stromal cells pre‐adapted to the heterogeneous extracellular pH (pH e ) in the tumor microenvironment. Cells residing in organs with net acid‐base transporting epithelia such as the pancreatic ductal and gastric epithelia are exposed to very different, temporally highly variable pH e values apically and basolaterally. This translates into spatially and temporally non‐uniform intracellular pH (pH i ) patterns. Disturbed pH e ‐ and pH i ‐homeostasis contributes to essentially all hallmarks of cancer. Our hypothesis, that the physiological pH e microenvironment in acid‐base secreting epithelia shapes cancers arising in these tissues, can be tested using novel imaging tools. The acidic tumor pH e in turn might be exploited therapeutically. Pancreatic cancers are used as our prime example, but we propose that this concept is also relevant for other cancers of acid‐base transporting epithelia.