Prostate cancer metastasis: role of the host microenvironment in promoting epithelial to mesenchymal transition and increased bone and adrenal gland metastasis.
BACKGROUND
The ARCaP cell line was established from the ascites fluid of a patient with metastatic prostate cancer. This study characterized the host microenvironmental role in cancer progression, epithelial to mesenchymal transition (EMT), and bone and adrenal metastasis in parental ARCaP and its derived cell subclones.


METHODS
Cytogenetic profiles, growth, migration, invasion, cellular interaction, drug sensitivities, and gene expression of ARCaP cell subclones were compared. In vivo gene expression, behavior, and metastasis of ARCaP subclones were analyzed by serial intracardiac injections into SCID mice.


RESULTS
ARCaP(E) cells, with cobblestone morphology, underwent EMT through cellular interaction with host bone and adrenal gland. Lineage-derived ARCaP(M) cells, with spindle-shape fibroblastic morphology, exhibited decreased cell adhesion and increased metastasis to bone and adrenal gland. Cytogenetic analyses of parental and ARCaP subclones confirmed their clonality.


CONCLUSIONS
ARCaP uniquely models the molecular basis of prostate cancer bone and adrenal metastases and epithelial to mesenchymal transition.
Xu
Jianchun
J
Department of Urology, Molecular Urology and Therapeutics Program, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Wang
Ruoxiang
R
Xie
Zhi Hui
ZH
Odero-Marah
Valerie
V
Pathak
Sen
S
Multani
Asha
A
Chung
Leland W K
LW
Zhau
Haiyen E
HE
D000230:Adenocarcinoma / Q000235:genetics / Q000556:secondary*; D000310:Adrenal Gland Neoplasms / Q000556:secondary*; D000818:Animals; D001859:Bone Neoplasms / Q000556:secondary*; D002448:Cell Adhesion; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D002999:Clone Cells; D018450:Disease Progression; D004777:Environment; D004847:Epithelial Cells / Q000473:pathology*; D006801:Humans; D008297:Male; D008648:Mesoderm / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000503:physiopathology; D009368:Neoplasm Transplantation; D009928:Organ Specificity / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured