Biology Reference
In-Depth Information
to as the “crooked tail syndrome,” is a severe phenotype, which, in addition to the
abnormal tail, includes general growth retardation and an abnormal skull shape.
It is not known whether this pronounced phenotypic consequence of uPARAP/
Endo180 deficiency, as compared with the situation in the mouse, reflects a differ-
ence in the physiological importance of the receptor in the two species, or whether
other factors are to be considered. Such factors could be the “challenge” in these
cattle represented by their oversized muscles, an unrecognized redundancy with
myostatin or even additional (unrecognized) redundant gene defects that may be
revealed in this inbred cattle strain as a result of a high degree of general homozy-
gosity. It may be noted that the crooked tail syndrome also includes an aberrant
muscular phenotype and that even cattle heterozygous for uPARAP/Endo180 defi-
ciency displayed a partial effect in this regard (Fasquelle et al.
2009
). This, however,
is not easily interpreted when considering the defective myostatin gene present in the
whole population of this strain of cattle.
A number of studies have addressed the expression of uPARAP/Endo180 in
cancer tissue. In invasive ductal carcinoma of the human breast, a pronounced
upregulation of uPARAP/Endo180 was evident in myofibroblasts and the receptor
was also present in some tumor-associated macrophages (Schnack Nielsen et al.
2002
). Importantly, the tumor cells were in all cases uPARAP/Endo180-negative in
this study. However, in a rare type of cancer, basal-like breast cancer in which the
tumor cells have a protein expression pattern resembling that of myoepithelial cells,
the cancer cells were found to be positive for uPARAP/Endo180 in some cases
(Wienke et al.
2007
). This is in line with the finding that myoepithelial cells are
indeed uPARAP/Endo180-positive in ductal carcinoma in situ (Schnack Nielsen
et al.
2002
) and, in some cases, also in normal breast tissue (Wienke et al.
2007
).
The expression of uPARAP/Endo180 has also been studied in head and neck
squamous cell carcinoma. In this case, an upregulation of the protein was found
in fibroblast-like stromal cells, with the poorly differentiated tumors showing the
stronger stromal expression (Sulek et al.
2007
). In prostate cancer, an immunofluo-
rescence-based study pointed to an upregulation of uPARAP/Endo180 in both the
epithelial and the stromal compartment although the specificity of immunostaining
was not rigorously verified (Kogianni et al.
2009
).
The localization of uPARAP/Endo180 in the tumor stroma, as well as the
importance of matrix turnover during cancer invasion, has prompted studies on the
functional role of this receptor in cancer invasion. In one investigation, uPARAP/
Endo180-deficient mice were crossed into a genetic tumor model, the MMTV-PymT
system, in which mice develop spontaneous malignant mammary tumors. When
comparing uPARAP/Endo180 expressing and uPARAP/Endo180-deficient PymT
mice in a littermate-controlled setting, the deficiency proved responsible for a
significant decrease in primary tumor growth (Curino et al.
2005
). Whereas this
delay was only moderate, the same study revealed a very striking difference by
histological examination of the tumors. The uPARAP/Endo180-deficient mice
contained large accumulations of collagen in the tumors, whereas this material had
been efficiently cleared in the uPARAP/Endo180-expressing littermates.
