Role of monocyte-lineage cells in prostate cancer cell invasion and tissue factor expression.
BACKGROUND
Tissue factor (TF) is a cell surface glycoprotein intricately related to blood coagulation and inflammation. This study was performed to investigate the role of monocyte-lineage cells in prostate cancer cell TF expression and cell invasion.


METHODS
Prostate cancer cell invasion was tested with and without added peripheral blood monocytes or human monocyte-lineage cell lines. TF neutralizing antibodies were used to determine the TF requirement for prostate cancer cell invasion activity. Immunohistochemistry was performed to identify prostate tissue CD68 positive monocyte-derived cells and prostate epithelial TF expression.


RESULTS
Co-culture of PC-3, DU145, and LNCaP cells with isolated human monocytes significantly stimulated prostate cancer cell invasion activity. TF expression was greater in highly invasive prostate cancer cells and was induced in PC-3, DU145, and LNCaP cells by co-culture with U-937 cells, but not with THP-1 cells. TF neutralizing antibodies inhibited PC-3 cell invasion in co-cultures with monocyte-lineage U-937 or THP-1 cells. Prostate cancer tissues contained more CD68 positive cells in the stroma and epithelium (145 ± 53/mm(2)) than benign prostate (108 ± 31/mm(2)). Samples from advanced stage prostate cancer tended to contain more CD68 positive cells when compared with lower stage lesions. Prostatic adenocarcinoma demonstrated significantly increased TF expression compared with benign prostatic epithelium.


CONCLUSIONS
This study shows that co-culture with monocyte-lineage cells induced prostate cancer cell invasion activity. PC-3 invasion and TF expression was induced in co-culture with U-937 cells and partially inhibited with TF neutralizing antibodies.
Lindholm
Paul F
PF
Department of Pathology, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA. p-lindholm@northwestern.edu
Lu
Yi
Y
Adley
Brian P
BP
Vladislav
Tudor
T
Jovanovic
Borko
B
Sivapurapu
Neela
N
Yang
Ximing J
XJ
Kajdacsy-Balla
André
A
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D018920:Coculture Techniques; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009000:Monocytes / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000378:metabolism; D018709:Statistics, Nonparametric; D013925:Thromboplastin / Q000096:biosynthesis*; D046888:Tissue Array Analysis
C488033:C5AR1 protein, human; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D013925:Thromboplastin