TY - JOUR
T1 - The regulation of prostate cancer cell adhesion to human bone marrow endothelial cell monolayers by androgen dihydrotestosterone and cytokines
AU - Cooper, Carlton R.
AU - Bhatia, Jasmine K.
AU - Muenchen, Heather J.
AU - McLean, Lisa
AU - Hayasaka, Satoru
AU - Taylor, Jeremy
AU - Poncza, Paul J.
AU - Pienta, Kenneth J.
N1 - Funding Information:
We are grateful to Mark Kukuruga, Ann Marie Des Lauriers and Karen Peterson of the Flow Cytometry Core at the University of Michigan for technical support. We are also grateful to Dr Hal Weidner for editorial assistance. This work was supported by the SPORE grant at The University of Michigan Comprehensive Cancer Center Ref # P50 CA 69568 and Comprehensive Cancer Grant Ref # CA 46592. Dr
Funding Information:
Cooper is supported by a 1999 American Foundation for Urological Disease Fellowship (Zeneca Pharmaceuticals). Dr Muenchen is supported by The University of Michigan Comprehensive Cancer Center Urology Training Grant. Dr Pienta is supported, in part, by CaPCURE.
PY - 2002
Y1 - 2002
N2 - A previous study from our laboratory suggested that prostate cancer metastasis to bone may be mediated, in part, by preferential adhesion to human bone marrow endothelial (HBME) cells. Tumor cell adhesion to endothelial cells may be modulated by the effect of cytokines on cell adhesion molecules (CAMs). Tumor necrosis factor-alpha (TNF-α) regulates VCAM expression on the endothelium and this effect is enhanced by dihydrotestosterone (DHT). Transforming growth factor-beta (TGF-β) stimulates the expression of α2β1integrin on PC-3 cells. The current study investigated the effects of the above cytokines and DHT (singularly and in various combinations) upon HBME and prostate cancer cell expression of VCAM, α2 integrin subunit, and β1 integrin subunit by flow cytometry. We also monitored the effects of the above treatments on PC-3 cell adhesion to HBME monolayers. The data demonstrate that none of the treatments significantly altered the expression of selected CAMs on HBME cell and neoplastic prostate cell lines. The treatment of HBME monolayers with various combinations of cytokines and DHT prior to performing adhesion assays with PC-3 demonstrates that treatments containing TGF-β reduced PC-3 cell adhesion to HBME monolayers by 32% or greater (P < 0.05). The reduction in PC-3 cell adhesion to TGF-β-treated HBME monolayers was dose dependent. Interestingly, LNCaP cells but not PC-3 cells treated with TGF-β had a reduced ability to adhere to untreated HBME monolayers. These results suggest that TGF-β may reduce tumor cell adhesion to bone marrow microvascular endothelium, in vivo. The biological significance of this observation is discussed.
AB - A previous study from our laboratory suggested that prostate cancer metastasis to bone may be mediated, in part, by preferential adhesion to human bone marrow endothelial (HBME) cells. Tumor cell adhesion to endothelial cells may be modulated by the effect of cytokines on cell adhesion molecules (CAMs). Tumor necrosis factor-alpha (TNF-α) regulates VCAM expression on the endothelium and this effect is enhanced by dihydrotestosterone (DHT). Transforming growth factor-beta (TGF-β) stimulates the expression of α2β1integrin on PC-3 cells. The current study investigated the effects of the above cytokines and DHT (singularly and in various combinations) upon HBME and prostate cancer cell expression of VCAM, α2 integrin subunit, and β1 integrin subunit by flow cytometry. We also monitored the effects of the above treatments on PC-3 cell adhesion to HBME monolayers. The data demonstrate that none of the treatments significantly altered the expression of selected CAMs on HBME cell and neoplastic prostate cell lines. The treatment of HBME monolayers with various combinations of cytokines and DHT prior to performing adhesion assays with PC-3 demonstrates that treatments containing TGF-β reduced PC-3 cell adhesion to HBME monolayers by 32% or greater (P < 0.05). The reduction in PC-3 cell adhesion to TGF-β-treated HBME monolayers was dose dependent. Interestingly, LNCaP cells but not PC-3 cells treated with TGF-β had a reduced ability to adhere to untreated HBME monolayers. These results suggest that TGF-β may reduce tumor cell adhesion to bone marrow microvascular endothelium, in vivo. The biological significance of this observation is discussed.
KW - Dihydrotestosterone (DHT)
KW - Human bone marrow endothelial cells
KW - Human prostate cancer cells
KW - Transforming growth factor-β
KW - Tumor cell adhesion
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U2 - 10.1023/A:1013849123736
DO - 10.1023/A:1013849123736
M3 - Article
C2 - 11918080
AN - SCOPUS:0036191946
SN - 0262-0898
VL - 19
SP - 25
EP - 33
JO - Clinical and Experimental Metastasis
JF - Clinical and Experimental Metastasis
IS - 1
ER -