High gene expression of semaphorin 5A in pancreatic cancer is associated with tumor growth, invasion and metastasis

Authors

  • Anguraj Sadanandam,

    1. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE
    Search for more papers by this author
  • Michelle L. Varney,

    1. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE
    Search for more papers by this author
  • Seema Singh,

    1. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE
    2. Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE
    Search for more papers by this author
  • Abdelkader E. Ashour,

    1. Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE
    2. Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
    Search for more papers by this author
  • Nicolas Moniaux,

    1. Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE
    2. INSERM, U785, Faculté de Médecine, Centre Hépatobiliaire, Université Paris-Sud, Villejuif, France
    Search for more papers by this author
  • Shonali Deb,

    1. Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE
    Search for more papers by this author
  • Subodh M. Lele,

    1. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE
    Search for more papers by this author
  • Surinder K. Batra,

    1. Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE
    2. Eppley Cancer Center, University of Nebraska Medical Center, Omaha, NE
    Search for more papers by this author
  • Rakesh K. Singh

    Corresponding author
    1. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE
    2. Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE
    3. Eppley Cancer Center, University of Nebraska Medical Center, Omaha, NE
    • Department of Pathology and Microbiology, University of Nebraska Medical Center, 985900 Nebraska Medical Center, Omaha, NE 68198-5900, USA
    Search for more papers by this author
    • Tel.: +402-559-9949, Fax: +402-559-5900


Abstract

Semaphorin 5A (SEMA5A) is an axonal regulator molecule, which belongs to the Semaphorin family of proteins. Previously, we identified SEMA5A as a putative marker for aggressive pancreatic tumors. However, the expression, localization and functional significance of SEMA5A in pancreatic tumors remain unclear. In our study, we hypothesized that SEMA5A expression modulates pancreatic tumor growth and metastasis. We analyzed the constitutive expression and localization of SEMA5A in patient pancreatic tumors (n = 33) and unmatched normal pancreatic (n = 8) tissues and human pancreatic cancer cell lines (n = 16) with different histopathological characteristics. We observed significantly higher expression of SEMA5A protein expression (p < 0.05) in human pancreatic tumor tissue samples compared to normal pancreatic tissues. Similarly, the pancreatic cancer cell lines with higher tumorigenic and metastatic potentials as xenografts in nude mice expressed higher levels of SEMA5A mRNA compared to those with lower tumorigenic and metastatic potentials. Furthermore, we examined the functional role of SEMA5A in pancreatic tumor growth and invasion. Ectopic expression of mouse full-length Sema5A in Panc1 (SEMA5A negative) cells significantly (p < 0.05) enhanced tumorigenesis, growth and metastasis in vivo as well as proliferation, invasiveness and homotypic aggregation in vitro. Together, these data demonstrate that the expression of SEMA5A in pancreatic cancer cells regulates tumorigenesis, growth, invasion and metastasis, and it also suggests a novel target for diagnosis and treatment of pancreatic cancer.

Ancillary