Bioinformatics Analysis to Identify Cell Adhesion Molecules in Cancer - Adhesion Molecules - page 311

APPLICATION OF KNOWLEDGE
Cell-cell and cell-matrix adhesion are critical for various biological processes,
and CAMs mediate these processes. During tumor formation, progression and
metastasis, the tumor cell CAMs change their ability to bind to their neighboring
cells and/or the extracellular matrix. h e breaking and forming of bonds between
CAMs on the tumor and endothelial cells of the secondary organs is important
for the tumor cells to undergo local or distant metastasis. h ese cells express
unique CAMs on their surface for functional tumor progression and metastasis.
In contrast, relatively few CAMs have been identii ed as targets for clinical
diagnosis or the treatment of dif erent types of cancers. h erefore, the molecular
diversity of CAMs associated with dif erent types of tumor cell surfaces needs to
be understood. h is can be achieved using high-throughput technologies and
analyzing data using bioinformatics approaches. h is approach using appropriate
models for cancer might provide CAM targets on the surface of tumor cells that
could be used as diagnostic and therapeutic targets for tumors.
PHAGE DISPLAY LIBRARY
Organ-specii c homing of tumor cells suggests that the vasculature in dif erent
tissues is dif erent and indicates that organ microenvironments carry unique
CAMs accessible to circulating tumor cells (Pasqualini and Ruoslahti 1996,
Pasqualini 1999). In addition, tumor tissues express unique adhesion molecules
important for homing and organ-specii c colonization of tumor cells (Fidler and
Hart 1982, Sadanandam et al . 2007). Up until now, identii cation of tumor- and
organ-specii c adhesion molecules has progressed slowly, but several recent reports
have demonstrated the use of phage display libraries to identify unique CAMs in
the tumor and organ microenvironments (Arap et al . 1998, Sato et al . 2007).
Since its introduction in 1985 (Smith 1985), the phage display library has
developed into a very useful technique for studying protein-protein interactions.
Specii cally, ligand-binding regions are identii ed using the random peptide
library displayed on the surface of the coat proteins of genetically engineered
phage (Burritt et al . 1996, Cwirla et al . 1990). h e desired peptides are ai nity-
selected on the basis of their binding to target molecule by injecting a pool of
phages intravenously into mice (Figs. 1 and 2) or alternatively by binding to an
immobilized target on a solid surface (Koivunen et al . 1994). Multiple rounds
of ai nity selection (biopanning) enrich the highly specii c peptides that bind
to their targets. h is type of approach can yield tissue-specii c homing peptides
(Pasqualini and Ruoslahti 1996, Sadanandam et al . 2007). h e strength of this
technology is its ability to identify interactive regions of peptides and other
molecules without pre-existing notions about the nature of interactions. In this way,
billions of peptides can be ef ectively surveyed for tight binding to a given protein