Functional changes in murine mammary cancer cells elicited by CoCl2-induced hypoxia

Low O₂ levels in solid tumors are associated with increase in hypoxia-inducible factor 1α (HIF-1α). The present study examines functional changes involved in adaptation to hypoxia of the LMM3 mammary tumor cell line, using CoCl₂ as hypoxic mimetic. Our results showed that LMM3 cells were not only tolerant to 150 μM CoCl₂ but they can overgrowth in vitro respect to untreated cells. Hypoxia inhibited cell invasion, migration, MMP-9 activity and NO levels. Macrophage cytotoxicity augmented under hypoxia but was blunted by conditioned media from tumor cells. In vivo tumorigenicity of CoCl₂-treated cells was greater than controls. Our results show stabilization of HIF-1α in LMM3 cells under CoCl₂ and functional changes associated with enhanced cell survival and growth but not with tumor dissemination.