Receptor for hyaluronan-mediated motility isoform B promotes liver metastasis in a mouse model of multistep tumorigenesis and a tail vein assay for metastasis Journal Article
| Authors: | Du, Y. C. N.; Chou, C. K.; Klimstra, D. S.; Varmus, H. |
| Article Title: | Receptor for hyaluronan-mediated motility isoform B promotes liver metastasis in a mouse model of multistep tumorigenesis and a tail vein assay for metastasis |
| 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 (RHAMMB) promotes tumor growth and metastases to lymph nodes and the liver. The propensity of RHAMMB-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 RHAMMB, we found that RHAMMB 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 RHAMMB promotes hepatic metastasis by islet tumor cells, perhaps through growth factor receptor-mediated signaling. |
| Keywords: | immunohistochemistry; signal transduction; protein phosphorylation; unclassified drug; nonhuman; liver neoplasms; lymph node metastasis; cell proliferation; mouse; animals; mice; mus; stat3 protein; apoptosis; epidermal growth factor receptor; animal experiment; animal model; receptor, epidermal growth factor; phosphorylation; carcinogenesis; gene transfer; liver metastasis; blotting, western; reverse transcriptase polymerase chain reaction; gefitinib; immunoprecipitation; cell migration; mitogen activated protein kinase 1; mitogen activated protein kinase 3; stat3 transcription factor; receptor; enzyme-linked immunosorbent assay; tumor growth; gene transfer techniques; mitogen-activated protein kinase 3; antigens, cd44; extracellular matrix proteins; adenoma, islet cell; receptor for hyaluronan mediated motility isoform b; pancreas islet cell |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 108 |
| Issue: | 40 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2011-10-04 |
| Start Page: | 16753 |
| End Page: | 16758 |
| Language: | English |
| DOI: | 10.1073/pnas.1114022108 |
| PROVIDER: | scopus |
| PMCID: | PMC3189086 |
| PUBMED: | 21940500 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 2 November 2011" - "CODEN: PNASA" - "Source: Scopus" |
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