Effects of adipocytes on the proliferation and differentiation of prostate cancer cells in a 3-D culture model.
OBJECTIVE
To investigate how the mechanism of adipocyte-prostate cancer cell interaction affects the proliferation and differentiation of prostate cancer cells.


METHODS
An androgen-dependent cell line (LNCaP), two androgen-independent cell lines (PC-3, DU145), and mature adipocytes harvested from male Wistar rats were used. Cancer cells were co-cultured with the isolated mature adipocytes in 3-D collagen gel matrix culture. The morphology and proliferative ability of the prostate cancer cells were examined. With regard to the activation of the phosphatidylinositol 3-kinase (PI3K) pathway, the expression of phosphatase and tensin homologue deleted on chromosome ten (PTEN), Akt and Bad were determined by immunohistochemistry.


RESULTS
LNCaP cells co-cultured with adipocytes formed larger clusters than those of the control. PC-3 cells co-cultured with adipocytes did not form larger clusters, but formed spherical and spindle-shaped cells. The phosphorylation of Akt in PC-3 cells was greater in the co-cultured group compared with the controls, but there were no significant differences in the phosphorylation of Akt with regard to LNCaP and DU145 cells.


CONCLUSIONS
Adipocytes could modulate the proliferation and differentiation of prostate cancer cell lines. Activation of the PI3K pathway might be involved in the prostate cancer cell-adipocyte interaction.
Kaneko
Arata
A
Department of Urology, Faculty of Medicine, Saga University, Saga, Japan. kanekoa@cc.saga-u.ac.jp
Satoh
Yuji
Y
Tokuda
Yuji
Y
Fujiyama
Chisato
C
Udo
Kazuma
K
Uozumi
Jiro
J
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D017667:Adipocytes / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D051025:bcl-Associated Death Protein / Q000378:metabolism
C494819:BAD protein, human; D051025:bcl-Associated Death Protein; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human