Adiponectin receptor expression is elevated in colorectal carcinomas but not in gastrointestinal stromal tumors.
Circulating adiponectin is inversely associated with colorectal carcinoma. However, adiponectin receptor expression has not been examined in normal gastrointestinal tissue, colorectal malignancies, or gastrointestinal stromal tumors (GISTs). We collected 40 colorectal carcinomas and 12 non-tumor colorectal tissue specimens from patients with colorectal cancer, as well as 45 tumor and 13 non-tumor specimens from patients with GIST. Expression and localization of adiponectin receptors (AdipoR1 and AdipoR2) were assessed using immunohistochemistry. We also confirmed expression of adiponectin receptors using rtPCR in matched normal and colorectal cancer specimens obtained from five patients. Finally, we detected adiponectin receptors and assessed adiponectin signaling in three colon cancer cell lines. Adiponectin receptor expression, assessed by either rtPCR or immunohistochemistry, was present in normal tissue and was significantly lower than in colorectal carcinomas. Among carcinomas, 95% displayed positive or strongly positive expression of AdipoR1 and 88% of AdipoR2, versus 8% and 0%, respectively, for non-tumor specimens (P<0.0001). AdipoR1 expression assessed by rtPCR was 1.6-fold higher in tumor than in non-tumor tissue (P<0.05). In addition, we found that adiponectin at physiological concentrations can activate in vitro intracellular signaling pathways in three colon cancer cell lines, expressing both adiponectin receptors 1 and 2. No significant differences in expression of adiponectin receptors in tumor versus non-tumor GI specimens were detected among patients with GIST. Colon cancer cell lines express adiponectin receptors, through which adiponectin activates in vitro intracellular signaling pathways. Adiponectin receptors are also detected in normal GI tissue and their expression is elevated in colorectal carcinomas, but not in GIST.
Williams
Catherine J
CJ
Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Mitsiades
Nicholas
N
Sozopoulos
Elias
E
Hsi
Alex
A
Wolk
Alicja
A
Nifli
Artemissia-Phoebe
AP
Tseleni-Balafouta
Sofia
S
Mantzoros
Christos S
CS
D015153:Blotting, Western; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D012333:RNA, Messenger; D054419:Receptors, Adiponectin