Myoglobin expression in renal cell carcinoma is regulated by hypoxia.
Myoglobin is a member of the hemoprotein superfamily, which additionally includes hemoglobin, neuroglobin and cytoglobin. Cytoplasmic localized myoglobin functions as a radical scavenger and prevents hypoxia. Besides muscle tissue MB expression could also be observed in other tissues as well as in different types of cancer. For the correlation between the expression of myoglobin, hypoxia-inducible-factor-1α, and capillary density tissue of 86 different renal cell carcinomas were immunohistochemically stained with myoglobin-specific and hypoxia-inducible-factor-1α-specific antibodies as well as with CD31 antibody. Four different renal carcinoma cell lines were cultivated under hypoxic conditions and the expression of myoglobin and hypoxia-inducible-factor-1α was evaluated by real-time PCR and Western blot. Renal cell carcinoma including clear cell, papillary, and chromophobe subtypes expressed myoglobin with an inverse relationship to capillary density being highly significant for clear cell renal cell carcinoma. For hypoxia-inducible-factor-1α a significant correlation with capillary density could also be observed in clear cell RCC. In renal cell carcinoma cell lines hypoxia induced a significant increase of myoglobin expression up to 62 fold, whereas hypoxia-inducible-factor-1α only increased up to 5 fold. The PCR results of myoglobin expression could be confirmed by Western blot. Myoglobin seems to be a sensitive marker for hypovascularized tumor entities especially during the early phase of hypoxia. Such neoplasias may benefit from an antiangiogenic therapy.
Department of Pathology, University of Göttingen, Robert-Koch-Straße 40, 37075 Göttingen, Germany. Electronic address: clbehnes@med.uni-goettingen.de.
C L
CL
Behnes
J
J
Bedke
S
S
Schneider
S
S
Küffer
A
A
Strauss
F
F
Bremmer
P
P
Ströbel
H J
HJ
Radzun
D017209:Apoptosis; D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009211:Myoglobin / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009211:Myoglobin; D012333:RNA, Messenger
HIF-1α; Hypoxia; Myoglobin; Renal cell carcinoma