Identification of functional cell adhesion molecules with a potential role in metastasis by a combination of in vivo phage display and in silico analysis

Anguraj Sadanandam, Michelle L. Varney, Leo Kinarsky, Hesham H Ali, R Lee Mosley, Rakesh K Singh

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32 Citations (Scopus)

Abstract

Organ-specific homing of malignant cells involves interactions mediated through cell adhesion molecules and their receptors on the cell surface. Identification of peptides that mimic these receptor-ligand interactions is critical for analyzing the functional role of these proteins and is therapeutically significant to target or block organ-specific homing of tumor cells. Following three cycles of in vivo biopanning using a phage display peptide library injected into mice, we identified 11 unique peptides that were specific for homing to lung, liver, bone marrow, or brain. We developed a bioinformatics strategy to identify putative cell adhesion molecules (CAM) involved in tumor cell migration, invasion, and metastasis based on identified organ-specific peptides. Structural information, including surface exposure and the binding preference of any of these residues in the identified proteins, was examined. These studies resulted in identification of Semaphorin 5A (mouse, Sema5A; human, SEMA5A) and its receptor Plexin B3. The gene expression profile of these proteins in tumors and tumor cell lines was assessed using virtual microarray and serial analysis of gene expression (SAGE) databases and was further confirmed using reverse transcriptase polymerase chain reaction (RT-PCR). Our data demonstrate an association between the expression of SEMA5A and Plexin B3 and the aggressiveness of pancreatic and prostate cancer cells. In summary, using a combined experimental and bioinformatics approach, we have identified functional tumor-specific CAMs, which may be critical for organ-specific metastasis.

Original languageEnglish (US)
Pages (from-to)41-57
Number of pages17
JournalOMICS A Journal of Integrative Biology
Volume11
Issue number1
DOIs
StatePublished - Apr 24 2007

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Bacteriophages
Cell Adhesion Molecules
Computer Simulation
Tumors
Display devices
Neoplasm Metastasis
Cells
Computational Biology
Neoplasms
Bioinformatics
Gene expression
Peptides
Semaphorins
Peptide Library
Proteins
Peptide Receptors
Cell Surface Receptors
Microarray Analysis
Tumor Cell Line
Reverse Transcriptase Polymerase Chain Reaction

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

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title = "Identification of functional cell adhesion molecules with a potential role in metastasis by a combination of in vivo phage display and in silico analysis",
abstract = "Organ-specific homing of malignant cells involves interactions mediated through cell adhesion molecules and their receptors on the cell surface. Identification of peptides that mimic these receptor-ligand interactions is critical for analyzing the functional role of these proteins and is therapeutically significant to target or block organ-specific homing of tumor cells. Following three cycles of in vivo biopanning using a phage display peptide library injected into mice, we identified 11 unique peptides that were specific for homing to lung, liver, bone marrow, or brain. We developed a bioinformatics strategy to identify putative cell adhesion molecules (CAM) involved in tumor cell migration, invasion, and metastasis based on identified organ-specific peptides. Structural information, including surface exposure and the binding preference of any of these residues in the identified proteins, was examined. These studies resulted in identification of Semaphorin 5A (mouse, Sema5A; human, SEMA5A) and its receptor Plexin B3. The gene expression profile of these proteins in tumors and tumor cell lines was assessed using virtual microarray and serial analysis of gene expression (SAGE) databases and was further confirmed using reverse transcriptase polymerase chain reaction (RT-PCR). Our data demonstrate an association between the expression of SEMA5A and Plexin B3 and the aggressiveness of pancreatic and prostate cancer cells. In summary, using a combined experimental and bioinformatics approach, we have identified functional tumor-specific CAMs, which may be critical for organ-specific metastasis.",
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AU - Varney, Michelle L.

AU - Kinarsky, Leo

AU - Ali, Hesham H

AU - Mosley, R Lee

AU - Singh, Rakesh K

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