Impact of exogenous lactate on survival and radioresponse of carcinoma cells in vitro.
OBJECTIVE
Tumour lactate levels have been shown to correlate with high radioresistance in tumour models in vivo. The study aimed to evaluate the impact of pathophysiological extracellular lactate concentrations and acidosis on the in vitro survival and radioresponse of various cancer cell lines.


METHODS
HCT-116, HT29 (colorectal) and FaDu (HNSCC) carcinoma cells were studied. Lactate release rates were determined, and expression of the monocarboxylate transporter MCT1 and its cofactor CD147 were monitored by immunofluorescence and flow cytometry. Colony formation was compared for cells exposed to 20 mM exogenous lactate, acidosis (pH 6.4) and lactate plus acidosis relative to control and dose response curves (0.5-10 Gy) were documented.


RESULTS
All cell lines expressed MCT1 and CD147 and showed comparable lactate release rates. High lactate levels and acidosis slightly decreased HCT-116 colony forming capacity. This effect was neither additive nor did it affect radioresponse. Clonogenic survival of HT29 cells, however, was critically reduced in a lactate-enriched or acidic milieu and a synergistic effect was observed. Here, both conditions enhanced radiosensitivity. Exogenous lactate also impaired colony formation of FaDu cells but acidosis was ineffective. This cell line was more susceptible to irradiation under lactate exposure independent of pH.


CONCLUSIONS
Tumour cell behaviour and radioresponse in a lactate environment is multifaceted. The consideration of lactate accumulation as a parameter affecting radiotherapeutic intervention and as a target for new therapeutic strategies is interesting but requires extended mechanistic studies.
Grotius
Janine
J
Tumor Pathophysiology, OncoRay - Center for Radiation Research in Oncology, Faculty of Medicine Carl Gustav Carus, TU Dresden, Germany.
Dittfeld
Claudia
C
Huether
Melanie
M
Mueller-Klieser
Wolfgang
W
Baumann
Michael
M
Kunz-Schughart
Leoni A
LA
D000138:Acidosis / Q000378:metabolism / Q000473:pathology; D051926:Basigin / Q000378:metabolism; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects*; D005947:Glucose / Q000378:metabolism; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000378:metabolism / Q000494:pharmacology*; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D011836:Radiation Tolerance / Q000187:drug effects*; D027981:Symporters / Q000378:metabolism; D014410:Tumor Stem Cell Assay; D000099233:Monocarboxylate Transport Protein 1
D051926:Basigin; D005947:Glucose; D019344:Lactic Acid; D027501:Monocarboxylic Acid Transporters; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C497886:BSG protein, human