Effects of tumour acidification with glucose+MIBG on the spontaneous metastatic potential of two murine cell lines.
In addition to hypoxia, acidic extracellular pH (pH(e)) is recognised as one of the microenvironmental characteristics of solid tumours. A number of studies have examined ways to increase tumour acidity in order to improve tumour-specific targeting of certain drugs and the effectiveness of hyperthermia. However, previous data have shown that exposure of murine tumour cells to acid conditions in culture can enhance their metastatic potential when injected subsequently into mice, raising the concern that deliberate tumour acidification might increase the probability of metastasis. In this study, we examined the effects of in vivo tumour acidification and hypoxia on the spontaneous metastatic potential of the murine KHT-C fibrosarcoma and B16F1 melanoma cell lines. A tumour-specific increase in extracellular acidity, demonstrated by measurements with pH electrodes, was achieved by daily intraperitoneal injections of meta-iodo-benzylguanidine (MIBG) and/or glucose. This method of tumour acidification during tumour growth did not significantly enhance the spontaneous metastatic potential of the two murine cell lines.
Kalliomäki
T
T
Experimental Therapeutics Division, Ontario Cancer Institute/Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
Hill
R P
RP
D019797:3-Iodobenzylguanidine / Q000494:pharmacology*; D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects; D005260:Female; D005354:Fibrosarcoma / Q000737:chemistry* / Q000188:drug therapy; D005947:Glucose / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008297:Male; D008546:Melanoma, Experimental / Q000737:chemistry* / Q000188:drug therapy; D051379:Mice; D009362:Neoplasm Metastasis / Q000473:pathology*; D014407:Tumor Cells, Cultured
D019797:3-Iodobenzylguanidine; D005947:Glucose