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.
The effects of CA IX catalysis products within tumor microenvironment / Alice Santi; Anna Caselli; Paolo Paoli; Denise Corti; Guido Camici; Giuseppe Pieraccini; Maria L Taddei; Sergio Serni; Paola Chiarugi; Paolo Cirri. - In: CELL COMMUNICATION AND SIGNALING. - ISSN 1478-811X. - ELETTRONICO. - 11:(2013), pp. 0-0. [10.1186/1478-811X-11-81]
The effects of CA IX catalysis products within tumor microenvironment
SANTI, ALICEInvestigation
;CASELLI, ANNAInvestigation
;PAOLI, PAOLOMembro del Collaboration Group
;CAMICI, GUIDOMembro del Collaboration Group
;PIERACCINI, GIUSEPPEMembro del Collaboration Group
;TADDEI, MARIA LETIZIAMembro del Collaboration Group
;SERNI, SERGIOMembro del Collaboration Group
;CHIARUGI, PAOLAMembro del Collaboration Group
;CIRRI, PAOLOSupervision
2013
Abstract
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.File | Dimensione | Formato | |
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