Pawel Swietach (UOXF)
Acidity is generally considered to be damaging to tissues yet it is a hallmark of cancer. We use a combination of fluorescence imaging, 2D and 3D culture/co-culture and mathematical modelling to explore how acidity (i.e. low pH) arises and is regulated in the tumour microenvironment, and how it exerts a signalling role on cellular processes, including those related to disease progression. These scientific questions are challenging because acid/base balance is determined by a complex interplay between membrane transport, diffusion, buffering and metabolic production.
On the cover: Co-culture of colon HCT116 cancer cells with normal skin NHDF fibroblasts. /Red/, cSNARF1 excited at 555 nm. /Green/, green fluorescent protein (expressed in fibroblasts only) excited at 480 nm. The striking differences in intracellular carbonic anhydrase activity between these two cell types (high activity in cancer cell) can give rise to differences in coupling between CO2 partial pressure (/e.g./ blood flow) and pH-sensitive intracellular signaling. For details see the article by Hulikova /et al./, pages 25418–25430 <http://www.jbc.org/lookup/volpage/289/25418?iss=37>.
Hulikova A, Aveyard N, Harris AL, Vaughan-Jones RD, Swietach P. Intracellular Carbonic Anhydrase Activity Sensitizes Cancer Cell pH Signaling to Dynamic Changes in CO2 Partial Pressure. J Biol Chem. 2014 Sep 12;289(37):25418-30.
Hulikova A, Swietach P. Rapid CO2 permeation across biological membranes: implications for CO2 venting from tissue. FASEB J. 2014 Jul;28(7):2762-74.
Hulikova A, Harris AL, Vaughan-Jones RD, Swietach P. Regulation of intracellular pH in cancer cell lines under normoxia and hypoxia. J Cell Physiol. 2013 Apr;228(4):743-52.
Hulikova A, Vaughan-Jones RD, Swietach P. Dual role of CO2/HCO3- buffer in the regulation of intracellular pH of three-dimensional tumor growths. J Biol Chem. 2011 Apr 22;286(16):13815-26.
Swietach P, Patiar S, Supuran CT, Harris AL, Vaughan-Jones RD. The role of carbonic anhydrase 9 in regulating extracellular and intracellular pH in three-dimensional tumor cell growths. J Biol Chem. 2009 Jul 24;284(30):20299-310.
Swietach P, Wigfield S, Cobden P, Supuran CT, Harris AL, Vaughan-Jones RD. Tumor-associated carbonic anhydrase 9 spatially coordinates intracellular pH in three-dimensional multicellular growths. J Biol Chem. 2008 Jul 18;283(29):20473-83.