Stromal cell-derived factor-1 expression in pituitary adenoma tissues and upregulation in hypoxia.
The chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) is known to have a homing effect, recruiting endothelial progenitor cells (EPCs) from the bone marrow to ischemic foci. In this study, we investigated whether SDF-1 is triggered by hypoxia and might be a major driving force for tumor angiogenesis in pituitary adenomas. SDF-1 and microvascular density (MVD) were detected by double-immunofluorescence microscopy in CD34-positive vessels from 59 cases with pituitary adenomas. In vitro secretion of SDF-1 by the AtT20 mouse pituitary adenoma cell line under hypoxic conditions was quantitatively analyzed by ELISA, and SDF-1 mRNA levels were determined by real-time RT-PCR. Double-fluorescence immunohistochemistry showed that increases in MVD were significantly correlated with increased SDF-1 grade (P < 0.0001), and, concomitantly, the expression of SDF-1 was significantly greater in macroadenomas (P = 0.0203). SDF-1 secretion was inversely related to oxygen levels, with more severe degrees of hypoxia inducing greater levels of SDF-1 secretion. Real-time RT-PCR demonstrated that the SDF-1 mRNA level in AtT20 cells was significantly increased at 1% oxygen (logarithmic mean value = 1.55 +/- 0.56) compared with that at 21% oxygen. The current study strongly suggests that SDF-1 is a crucial angiogenic factor in pituitary adenomas, where it acts as a homing agent to mediate the mobilization of CD34-positive endothelial progenitor cells to the tumor parenchyma under hypoxic conditions.
Nomura
Ryutaro
R
Department of Neurosurgery, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
Yoshida
Daizo
D
Teramoto
Akira
A
D000236:Adenoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D054377:Chemokine CXCL12; D012333:RNA, Messenger