Adiponectin inhibits the growth and peritoneal metastasis of gastric cancer through its specific membrane receptors AdipoR1 and AdipoR2.
Adiponectin, a circulating peptide hormone produced in adipose tissue, has been shown to be reduced in the plasma of patients with cancer, suggesting that this adipokine may be mechanically involved in the pathogenesis of adiposity-related carcinogenesis. In this study, we examined the expression of adiponectin receptors (AdipoR1 and AdipoR2) and assessed the function of adiponectin in gastric cancer. All of the six gastric cancer cell lines significantly expressed mRNA and protein of both receptors with variable levels. Addition of 30 microg/mL adiponectin potently induced apoptosis and inhibited the proliferation of AZ521 and HCG27. Down-regulation of either AdipoR1 or AdipoR2 by specific siRNA significantly suppressed the growth inhibitory effects of adiponectin in both cell lines. Moreover, a local injection of adiponectin markedly inhibited the growth of AZ521 inoculated subcutaneously in nude mice. Similarly, the continuous intraperitoneal infusion of adiponectin effectively suppressed the development of peritoneal metastasis of AZ521. Adiponectin negatively regulates the progression of gastric cancer cells possibly through both AdipoR1 and AdipoR2. Although adiponectin was already reported to have antiangiogenic effects, our results suggest that the antitumor effect of adiponectin was, at least partially, dependent on the direct effects on tumor cells.
Ishikawa
Makoto
M
Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Kitayama
Joji
J
Yamauchi
Toshimasa
T
Kadowaki
Takashi
T
Maki
Toshiyuki
T
Miyato
Hideyo
H
Yamashita
Hiroharu
H
Nagawa
Hirokazu
H
D052242:Adiponectin / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D034741:RNA, Small Interfering / Q000235:genetics; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000098:blood supply / Q000473:pathology*
C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D034741:RNA, Small Interfering; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins