Biomedical Engineering Reference
In-Depth Information
Table 2 Examples of Hh transduction in human cancers
Tumor
Authors
Notes
Adenocarcinoma
of the biliary
tree
Berman et al. (2003)
Cyclopamine and Hh blocking antibody
inhibit cancer cell line proliferation
Adenocarcinoma
of the
esophagus
Berman et al. (2003)
Cyclopamine and Hh blocking antibody
inhibit cancer cell line proliferation
Adenocarcinoma
of the stomach
Berman et al. (2002)
Cyclopamine and Hh blocking antibody
inhibit cancer cell line proliferation
Medulloblastoma
of the brain
Berman et al. (2002)
Inactivation of Ptch leads to cancer growth
and cyclopamine inhibits cancer allograft
and cell line growth
Oral squamous
cell carcinoma
Nishimaki et al. (2004)
Cyclopamine inhibits cancer cell line
proliferation
Small cell lung
cancer
Watkins et al. (2003)
Cyclopamine and Hh blocking antibody
inhibit cancer cell line proliferation and
xenograft growth
1999; Bitgood and McMahon, 1995; Reddy et al., 2001; Heemskerk and
DiNardo, 1994; Silva-Vargas et al., 2005; Iwatsuki et al., 2007). In cancer the
link between Wnt and Hh is also well established (Tables 1 and 2), as shown by
van den Brink et al.; their experiments elegantly demonstrated that Ihh is a
negative regulating factor of Wnt during epithelial differentiation in the colon
(van den Brink et al., 2004). Proliferation of colorectal cancer cells throughWnt
suppression occurred through Gli-1 (Akiyoshi et al., 2006). Another group
found that Gli-1 was able to inhibit Wnt through SFRP-1, an antagonist of
Wnt and a transcriptional target of Hh (Akiyoshi et al., 2006). As the intricacies
of Hh are understood newer cues on how this developmental pathway interacts
with Wnt are brought to light; in turn this knowledge will aid understanding
how the function of pluripotent and progenitor pulmonary cells is regulated.
Evidence regarding the interplay between Wingless and Notch was first
discovered in the context of wing patterning and development in Drosophila
(Couso and Martinez Arias, 1994; Hing et al., 1994). Initially they synergize in
the early formation of the wing primordium. Later, Notch enhances wingless
expression at the future wing margin (Diaz-Benjumea and Cohen, 1995;
Neumann and Cohen, 1996). The detailed genetic experiments in organisms
such as Drosophila that led to the discovery of some crucial mechanisms of
interaction between Wnt and Notch are not possible in vertebrates due to
technical and logistic reasons. However, despite the limitations, there is evi-
dence that in vertebrates also, mutual interactions between Notch and Wingless
do occur during somitogenesis and muscle formation (Aulehla et al., 2003;
Aulehla andHerrmann, 2004), during the formation of skin precursors (Estrach
et al., 2006), and during the patterning of rhombomeres (Cheng et al., 2004).
