The effects of CA IX catalysis products within tumor microenvironment

Cell Communication and Signaling

Research

Giuseppe Pieraccini¹  Sergio Serni²  Maria Letizia Taddei³  Paola Chiarugi³  Paolo Paoli³  Alice Santi³  Anna Caselli³  Guido Camici³  Denise Corti³  Paolo Cirri³ 

[1] CISM Centro di servizi di Spettrometria di Massa, Università degli Studi di Firenze, Viale G. Pieraccini 6, 50139, Firenze, Italy;Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Largo Brambilla 3, 50134, Firenze, Italy;Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Università degli Studi di Firenze, Viale Morgagni 50, 50134, Firenze, Italy;

关键词: Tumor microenvironment;    CA IX;    Extracellular pH;    Coculture;    Bicarbonate;    Cancer associated fibroblasts;    Tumor metabolism;   

DOI  :  10.1186/1478-811X-11-81

 received in 2013-09-04, accepted in 2013-10-21,  发布年份 2013

来源: Springer

【 摘 要 】

Solid tumors are composed of both cancer cells and various types of accessory cells, mainly fibroblasts, that collectively compose the so called tumor-microenvironment. Cancer-associated fibroblasts have been described to actively participate in cancer progression by establishing a cytokine-mediated as well as metabolic crosstalk with cancer cells. In the present paper we show that activated human fibroblasts are able to boost tumor cells proliferation and that this effect is greatly dependent on stromal carbonic anhydrase IX (CA IX) activity. In fact fibroblasts show a strong upregulation of CA IX expression upon activation by cancer cells, while CA IX products, protons and bicarbonate, exert differential effects on cancer cells proliferation. While acidification of extracellular pH, a typical condition of rapidly growing solid tumors, is detrimental for tumor cells proliferation, bicarbonate, through its organication, supplies cancer cells with intermediates useful to sustain their high proliferation rate. Here we propose a new kind of fibroblasts/tumor cells crosstalk within tumor microenvironment, mediated by stromal CA IX products, aimed to favor cancer cells growth, opening new perspectives on CA IX role in tumor microenvironment.

【 授权许可】

Unknown   
© Santi et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.