Biomedical Engineering Reference
In-Depth Information
FIgurE 16.1
SHG images of normal murine mammary tissue (a) and murine mammary tissue surrounding a
tumor (b).
TABLE 16.1 Descriptions of Tumor-Related Collagen I Structures
Category 1 TACS
Category 2 TACS
Category 3 TACS
• Region of dense collagen I
surrounding tumor
• Collagen fibers have no specific
alignment
• Tumors may be pre-palpable
• Collagen I fibers wrapped
around tumor
• Fibers appear stretched across a
relatively smooth tumor
boundary
• Tangential orientation of fibers
(approximately 0 o to tumor
boundary) predominant
• Collagen I fibers aligned normal
to tumor boundary
• Tumor boundary is of an irregular
shape in these regions
• Indicative of local invasion
through collective epithelial cell
migration
• Fibers aligned in the direction of
cell invasion (approximately 90 o to
tumor boundary)
Source: Content taken from Boyd NF et al. N Engl J Med 2007, 356(3):227-236.
TACS fall roughly into three categories (see Table 16.1 and Figure 16.2) [17]. Importantly, these col-
lagen changes have prognostic significance: the presence of TACS from category 3, TACS-3, is associated
with a significantly increased risk of relapse or death from breast cancer in patients [28].
16.1.4 collagen as a therapeutic target
Not only is collagen a potential clinical biomarker for breast cancer; an important future direction is to use
collagen changes as a therapeutic target. Knowing which signaling pathways are activated allows pharma-
cologic targets to be exploited. Moreover, drugs that target LOX, the crosslinking enzyme, can decrease
ECM stiffness, providing a possible treatment option [9,11]. The tumor microenvironment and colla-
gen content can also affect responses to therapy. Collagen has been shown to increase chemo-resistance
through interactions with integrins and inhibition of drug delivery due to increased density. Drug deliv-
ery can be impaired by collagen concentration and ECM stiffness in several ways, including increasing
interstitial fluid pressure, impeding the movement of large drugs or binding and sequestering of drugs [8].
Despite the known role of the stroma and breast density in breast cancer and the growing evidence of
collagen as a direct player in breast cancer invasion and progression, there are few, if any, clinical practices
that directly harness this information. This is due in part to a need for more knowledge about the specific
role that collagen plays in breast tumor progression. Perhaps the greatest need is technologies that not
only help researchers unravel the role of collagen, but that can also help clinicians exploit collagen-related
changes for clinical treatment. While collagen is the most abundant protein in the body and its role as the
glue of the body has been known for generations, it is only in the last few decades that collagen has become
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