Identification of EpCAM as a molecular target of prostate cancer stroma.
To delineate the molecular changes that occur in the tumor microenvironment, we previously performed global transcript analysis of human prostate cancer specimens using tissue microdissection and expression microarrays. Epithelial and stromal compartments were individually studied in both tumor and normal fields. Tumor-associated stroma showed a distinctly different expression pattern compared with normal stroma, having 44 differentially expressed transcripts, the majority of which were up-regulated. In the present study, one of the up-regulated transcripts, epithelial cell adhesion activating molecule, was further evaluated at the protein level in 20 prostate cancer cases using immunohistochemistry and a histomathematical analysis strategy. The epithelial cell adhesion activating molecule showed a 76-fold expression increase in the tumor-associated stroma, as compared with matched normal stroma. Moreover, Gleason 4 or 5 tumor stroma was increased 170-fold relative to matched normal stroma, whereas the Gleason 3 tumor area showed only a 36-fold increase, indicating a positive correlation with Gleason tumor grade. Since the stromal compartment may be particularly accessible to vascular-delivered agents, epithelial cell adhesion activating molecule could become a valuable molecular target for imaging or treatment of prostate cancer.
Pathogenetics Unit, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4605, USA.
Sumana
S
Mukherjee
Annely M
AM
Richardson
Jaime
J
Rodriguez-Canales
Kris
K
Ylaya
Heidi S
HS
Erickson
Audrey
A
Player
Ernest S
ES
Kawasaki
Peter A
PA
Pinto
Peter L
PL
Choyke
Maria J
MJ
Merino
Paul S
PS
Albert
Rodrigo F
RF
Chuaqui
Michael R
MR
Emmert-Buck
D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D000071858:Epithelial Cell Adhesion Molecule; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule