Alpha 2-HS glycoprotein (fetuin-A) modulates murine skin tumorigenesis.
Fetuin, a major serum glycoprotein secreted by the liver, has been shown to play a role in bone development, calcium homeostasis and insulin sensitivity. In an earlier study, we demonstrated that bovine fetuin can bind to the plasma membrane of squamous and spindle-cell carcinoma cells. To test our hypothesis that fetuin plays a causal role in skin tumorigenesis, fetuin-A null and wild-type mice were challenged using a two-stage chemically-induced carcinogenesis protocol with DMBA (7,12-dimethylbenzo(a)anthracene) as the initiator, followed by twice weekly treatments with the tumor promoter TPA (12-O-tetradecanoylphorbol-13-acetate). Tumors that developed on fetuin-A null animals grew at a similar rate as those arising on their wild-type counterparts. Absence of fetuin-A did not alter tumor onset or conversion to squamous cell carcinoma, but reduced the number of tumors per mouse by 30%. This correlated with a decrease in tumor burden in fetuin-A null animals compared to wild-type weeks 18-22 from tumor onset. In addition, tumors arising on fetuin-A null mice had a diminished proliferative index with no change in cell survival or neovascularization in comparison with wild-type tumors. Our results suggest that fetuin-A contributes to early stages of skin tumorigenesis.
Leite-Browning
Maria L
ML
Department of Cancer Biology, Meharry Medical College, Vanderbilt University, Nashville, TN 37208, USA. mllbahia@aol.com
McCawley
Lisa J
LJ
Jahnen-Dechent
Willi
W
King
Lloyd E
LE
Matrisian
Lynn M
LM
Ochieng
Josiah
J
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D012867:Skin / Q000187:drug effects / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology; D060749:alpha-2-HS-Glycoprotein
C556357:Ahsg protein, mouse; D001798:Blood Proteins; D060749:alpha-2-HS-Glycoprotein; D015127:9,10-Dimethyl-1,2-benzanthracene; C032975:12-O-tetradeca-2,4,6,8-tetranoylphorbol-13-acetate; D013755:Tetradecanoylphorbol Acetate