Biomedical Engineering Reference
In-Depth Information
resistances to tamoxifen in cell lines and mouse models [53]. MMP9,
as mentioned above, is a matrix metalloproteinase that degrades
extracellular matrix (ECM) proteins and may be upregulated by
TGFβ signaling [54]. COL42A, another ECM protein mentioned in
previous section, may also be involved in the metastasis process.
While EMT is thought to mitigate the first steps of metastasis, the
reverse process, mesenchymal to epithelial transition (MET) is
required to establish the tumor cells in their distal locations. Re-
depositing basement membrane protein at that time is consistent
with re-establishing cell polarity, and the surrounding stromal
environment. The WNT signaling pathway has also been implicated
in EMT. WISP1, a downstream signaling molecule of WNT pathway,
is expressed in fibroblasts and is thought to promote tumor cell
migration as well as prevent apoptosis [55]. The role of EBF4 gene
in EMT is unknown. However, it is a transcription factor involved in
neuronal development, and therefore may modulate at least some
part of the EMT process [56].
After tumor cells undergo EMT, they intravasate into blood vessels,
extravasate to the metastatic site, initiate and sustain angiogenesis
and through the process continue to survive through anti-apoptotic
signals. Several proteins related to angiogenesis have already been
described (see Fig. 14.2) including FLT1, FGF18, COL4A2, and MMP9.
Other relevant proteins include: GPR180, a G protein-coupled
receptor, which regulates vascular remodeling [57]; GPR126, a G
protein-coupled receptor that is increased in human umbilical vein
endothelial cells; ESM1, a protein secreted in endothelial cells [58],
and SCUBE2, a developmental protein expressed in the vascular
endothelium [59]. The role of these proteins in metastasis has yet to
be elucidated.
14.7
Potential Advantages of MammaPrint as a
Prognostic Test
Approximately 30% of node-negative patients will need
chemotherapy to reduce the risk of recurrence. Currently, 47% of
breast cancer patients in the US are identified as node-negative
at the time of diagnosis; this could reach to 60-70% worldwide
in regions with widespread breast cancer screening and disease
awareness [60]. As the tumor biology is inherited in individual
