Abstract
The metastatic organotropism has been one of the cancer's greatest mysteries since the 'seed and soil' hypothesis. Although the role of EGFR in cancer cells is well studied, the effects of secreted EGFR transported by exosomes are less understood. Here we show that EGFR in exosomes secreted from gastric cancer cells can be delivered into the liver and is integrated on the plasma membrane of liver stromal cells. The translocated EGFR is proved to effectively activate hepatocyte growth factor (HGF) by suppressing miR-26a/b expression. Moreover, the upregulated paracrine HGF, which binds the c-MET receptor on the migrated cancer cells, provides fertile 'soil' for the 'seed', facilitating the landing and proliferation of metastatic cancer cells. Thus, we propose that EGFR-containing exosomes derived from cancer cells could favour the development of a liver-like microenvironment promoting liver-specific metastasis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3' Untranslated Regions / genetics
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Base Sequence
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Cell Line, Tumor
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Cell Membrane / metabolism
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Cell Proliferation
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Cells, Cultured
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Cellular Microenvironment*
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ErbB Receptors / metabolism*
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Exosomes / metabolism*
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Exosomes / ultrastructure
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Gene Expression Regulation, Neoplastic
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Hepatocyte Growth Factor / genetics
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Hepatocyte Growth Factor / metabolism
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Humans
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Liver / metabolism*
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Liver / pathology
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Liver Neoplasms / genetics
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Liver Neoplasms / pathology
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Liver Neoplasms / secondary*
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MicroRNAs / genetics
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MicroRNAs / metabolism
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Neoplasm Invasiveness
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Proto-Oncogene Proteins c-met / metabolism
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Stomach Neoplasms / blood
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Stomach Neoplasms / genetics
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Stomach Neoplasms / pathology*
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Up-Regulation / genetics
Substances
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3' Untranslated Regions
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HGF protein, human
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MIRN26A microRNA, human
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MicroRNAs
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Hepatocyte Growth Factor
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ErbB Receptors
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Proto-Oncogene Proteins c-met