High-throughput Computational and Experimental Biology Strategies for Identifying Tumor Expressing CAMs
Anguraj Sadanandam, Michelle L. Varney, and Rakesh K. Singh
University of Nebraska Medical Center, Omaha, NE-68198

Background: Organ-specific homing of tumor cells includes receptor-ligand interactions of cell adhesion molecules (CAMs), which stimulate or inhibit the cellular growth. Identifying CAMs from short peptides that mimic these protein-protein interactions has therapeutic significance in targeting or blocking the organ-specific metastasis.
Methods: Sequence and pattern analysis were applied to identify unique CAMs with organ-specific peptides as query against mouse genome and proteome sequences. The peptides were seven amino acids in length, and were affinity selected against specific organs utilizing in vivo phage display peptide library in NOD-SCID mice. Various databases were used for the analyses including Local Mouse Cell Adhesion Molecule (LMCAM) database developed by keyword search. Later to confirm the finding of novel protein-protein interactions involved in cancer, the structural and expression information of the identified proteins in cancer cell lines were examined using databases and experimental strategy.
Results: Thirty annotated CAMs corresponding to eleven different organ-specific peptides were identified using the bioinformatics analysis. One such identified protein, SEMA5A is reported for the first time to be expressed in human pancreatic cancer cell lines.
Conclusion: This combined strategy of experimental and computation biology is an initial approach in identifying novel tumor-specific molecules, thereby paving the way for complete understanding of their roles in various processes of tumor metastasis and making organ-specific targeting possible using these peptides.