Biomedical Engineering Reference
In-Depth Information
3.3.1.1.1 Healthy Tissues. Observations of GCPII expression in normal
tissues are summarized in Table 3.2. With the use of antibodies that are
more sensitive than 7E11 and recognize the extracellular GCPII domain, a
broader expression profile of GCPII became apparent. Of these studies, only
three attempted to quantify GCPII tissue distribution.
7,29,30
Sokoloff et al.
report significantly higher GCPII levels in prostate (approximately 300-4000
ng/mg of total protein) compared to levels in non-prostatic tissues which are
two orders of magnitude lower. Such a quantitative distinction in GCPII
levels in prostate/non-prostatic tissue was not, however, observed in the
study by Rovenska et al.
29
Some studies detected GCPII in the serum of healthy and/or prostate cancer
patients using 7E11 and/or 3F5.4C6 antibodies,
31-33
while others questioned
these results.
34,35
This issue remains unresolved.
3.3.1.1.2 Malignant Tissues. Early studies detected GCPII almost solely in
prostate tissue—benign as well as malignant.
1,35-39
GCPII was also detected
in metastases to the lymph nodes and bone.
1,38,39
GCPII levels are lowest in
benign prostate tissue, highest in malignant tissue, and intermediate in
intraepithelial neoplasia; the GCPII positivity has been reported in secretory-
acinar epithelium.
5,36,37
GCPII expression has been reported in numerous other cancers, including
kidney, bladder, breast, colon, and lung cancers.
4,28,30,40-43
3.3.1.1.3 Neovasculature. GCPII is expressed abundantly in the neovascu-
lature of most non-prostatic solid tumors, including tumors of the bladder,
breast, kidney, lung, testis, pancreas, and colon as well as melanoma and sar-
coma.
4,5,38,40,41,43-45
Interestingly, little or no GCPII expression was found in
neovasculature associated with prostate cancer.
5,36,38
While GCPII localiza-
tion in physiological neovasculature (such as granulation tissue and endome-
trium) remains unclear, GCPII expression in tumor neovasculature suggests
that it might be associated with an angiogenic factor.
3.3.1.2 Animal Models
GCPII is a ubiquitous protein found in many classes of organisms.
46
GCPII
orthologs in some common pharmaceutical model organisms have been par-
tially characterized—most extensively in mouse (Mus musculus), rat (Rattus
norvegicus), and pig (Sus scrofa). The amino acid sequence similarity of all of
these with human GCPII is around 90%.
47-49
Mouse, rat, and porcine GCPIIs have been cloned and characterized by a
number of researchers. Enzyme activity and inhibition studies showed that all
these orthologs could serve as model approximations of human GCPII in
enzymological studies.
2,29,47-50
On the other hand, these organisms vary in tissue
distribution pattern. Interestingly, little to no GCPII expression was found in
mouse, rat, pig, dog, and monkey prostate.
25,29,47,51
GCPII gene expression in
