Receptor for hyaluronan-mediated motility isoform B promotes liver metastasis in a mouse model of multistep tumorigenesis and a tail vein assay for metastasis Academic Article uri icon

Overview

MeSH Major

  • Adenoma, Islet Cell
  • Antigens, CD44
  • Extracellular Matrix Proteins
  • Liver Neoplasms
  • Signal Transduction

abstract

  • The gene encoding the receptor for hyaluronan-mediated motility (RHAMM) is overexpressed in many human cancers. However, it is unclear whether RHAMM plays a causal role in tumor initiation or progression. Using somatic gene transfer in a mouse model of islet cell tumorigenesis, we demonstrate that RHAMM isoform B (RHAMM(B)) promotes tumor growth and metastases to lymph nodes and the liver. The propensity of RHAMM(B)-expressing cells to metastasize to the liver was confirmed using an experimental metastasis assay in which cells were injected into the tail vein of immunodeficient mice. However, RHAMM(B) did not increase cell migration or proliferation in culture. In initial efforts to identify signaling pathways activated by RHAMM(B), we found that RHAMM(B) induced phosphorylation of epidermal growth factor receptor (EGFR), Erk1/2, and STAT3 and conferred susceptibility to apoptosis after treatment with an EGFR inhibitor, gefitinib. Taken together, the results indicate that RHAMM(B) promotes hepatic metastasis by islet tumor cells, perhaps through growth factor receptor-mediated signaling.

publication date

  • October 4, 2011

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3189086

Digital Object Identifier (DOI)

  • 10.1073/pnas.1114022108

PubMed ID

  • 21940500

Additional Document Info

start page

  • 16753

end page

  • 8

volume

  • 108

number

  • 40