title: The effects of CA IX catalysis products within tumor microenvironment.
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.
authors.forename: Alice
authors.initials: A
authors.lastname: Santi
authors.forename: Anna
authors.initials: A
authors.lastname: Caselli
authors.forename: Paolo
authors.initials: P
authors.lastname: Paoli
authors.forename: Denise
authors.initials: D
authors.lastname: Corti
authors.forename: Guido
authors.initials: G
authors.lastname: Camici
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pieraccini
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Taddei
authors.forename: Sergio
authors.initials: S
authors.lastname: Serni
authors.forename: Paola
authors.initials: P
authors.lastname: Chiarugi
authors.affiliation: Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Università degli Studi di Firenze, Viale Morgagni 50, 50134 Firenze, Italy. paolo.cirri@unifi.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Cirri
mesh_terms: D000818:Animals; D002256:Carbonic Anhydrases / Q000378:metabolism*; D002384:Catalysis; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D005347:Fibroblasts / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D016513:Mice, SCID; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D017693:Sodium Bicarbonate / Q000378:metabolism; D059016:Tumor Microenvironment / Q000502:physiology*
chemical_list: D017693:Sodium Bicarbonate; D002256:Carbonic Anhydrases