Differential effects of leptin on the invasive potential of androgen-dependent and -independent prostate carcinoma cells.
Obesity has been linked with an increased risk of prostate cancer. The formation of toxic free oxygen radicals has been implicated in obesity mediated disease processes. Leptin is one of the major cytokines produced by adipocytes and controls body weight homeostasis through food intake and energy expenditure. The rationale of the study was to determine the impact of leptin on the metastatic potential of androgen-sensitive (LNCaP) cells as well as androgen-insensitive (PC-3 and DU-145) cells. At a concentration of 200 nm, LNCaP cells showed a significant increase (20% above control; P < .0001) in cellular proliferation without any effect on androgen-insensitive cells. Furthermore, exposure to leptin caused a significant (P < .01 to P < .0001) dose-dependent decrease in migration and invasion of PC3 and Du-145 prostate carcinoma cell lines. At the molecular level, exposure of androgen-independent prostate cancer cells to leptin stimulates the phosphorylation of MAPK at early time point as well as the transcription factor STAT3, suggesting the activation of the intracellular signaling cascade upon leptin binding to its cognate receptor. Taken together, these results suggest that leptin mediates the invasive potential of prostate carcinoma cells, and that this effect is dependent on their androgen sensitivity.
Deo
Dayanand D
DD
Department of Biochemistry, Louisiana State University Health Science Center, New Orleans, LA 70112, USA.
Rao
Ashwin P
AP
Bose
Saideep S
SS
Ouhtit
Allal
A
Baliga
Surendra B
SB
Rao
Shilpa A
SA
Trock
Bruce J
BJ
Thouta
Rajesh
R
Raj
Madhwa H G
MH
Rao
Prakash N
PN
D000728:Androgens / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020738:Leptin / Q000008:administration & dosage*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*
D000728:Androgens; D020738:Leptin