Functional changes in murine mammary cancer cells elicited by CoCl2-induced hypoxia.
Low O(2) levels in solid tumors are associated with increase in hypoxia-inducible factor 1alpha (HIF-1alpha). The present study examines functional changes involved in adaptation to hypoxia of the LMM3 mammary tumor cell line, using CoCl(2) as hypoxic mimetic. Our results showed that LMM3 cells were not only tolerant to 150 microM CoCl(2) 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 CoCl(2)-treated cells was greater than controls. Our results show stabilization of HIF-1alpha in LMM3 cells under CoCl(2) and functional changes associated with enhanced cell survival and growth but not with tumor dissemination.
Borenstein
Ximena
X
Immunobiology Department, Research Area, Institute of Oncology Angel H. Roffo, University of Buenos Aires, Argentina.
Fiszman
Gabriel L
GL
Blidner
Ada
A
Vanzulli
Silvia I
SI
Jasnis
María A
MA
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003035:Cobalt / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D003035:Cobalt; C018021:cobaltous chloride