Murine prostate cancer inhibits both in vivo and in vitro generation of dendritic cells from bone marrow precursors.
BACKGROUND
There is increasing evidence to suggest that dendritic cells (DC) are functionally impaired in tumor bearing hosts. However there is little or no data on the effects of murine prostate cancer (CaP) on DC generation from bone marrow precursors.


METHODS
Flow cytometry, mixed leukocyte reactions (MLR), and immunohistochemical analyses were used to characterize DC in CaP.


RESULTS
DC generated in the presence of CaP cell lines RM1 and the cell line C2 from the transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse in a Transwell system expressed significantly lower levels of DC differentiation markers. This effect was confirmed when TK-neo-transfected RM1 cells were directly added to DC cultures and eliminated 5 days later using gancyclovir (GCV). Furthermore, co-incubation of DC with CaP cells resulted in a decrease in the stimulatory capacity of DC to induce T cell proliferation in the MLR assay. These results were further confirmed in vivo in two different murine models of CaP: i) DC generated from mice intrafemorally injected with TK-neo-transfected RM1 cells; and ii) in DC generated from TRAMP mice.


CONCLUSIONS
The generation and function of DC are significantly suppressed in the CaP microenvironment in both in vivo and in vitro murine models.
Tourkova
Irina L
IL
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Yamabe
Kazuo
K
Foster
Barbara
B
Chatta
Gurkamal
G
Perez
Lori
L
Shurin
Galina V
GV
Shurin
Michael R
MR
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D030801:Animals, Genetically Modified; D002450:Cell Communication; D002454:Cell Differentiation; D002455:Cell Division; D003713:Dendritic Cells / Q000502:physiology*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000473:pathology*; D013601:T-Lymphocytes / Q000502:physiology; D014407:Tumor Cells, Cultured