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Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS.
- Source :
-
Molecular & cellular proteomics : MCP [Mol Cell Proteomics] 2013 Feb; Vol. 12 (2), pp. 343-55. Date of Electronic Publication: 2012 Nov 15. - Publication Year :
- 2013
-
Abstract
- Activating mutations in KRAS occur in 30% to 40% of colorectal cancers. How mutant KRAS alters cancer cell behavior has been studied intensively, but non-cell autonomous effects of mutant KRAS are less understood. We recently reported that exosomes isolated from mutant KRAS-expressing colon cancer cells enhanced the invasiveness of recipient cells relative to exosomes purified from wild-type KRAS-expressing cells, leading us to hypothesize mutant KRAS might affect neighboring and distant cells by regulating exosome composition and behavior. Herein, we show the results of a comprehensive proteomic analysis of exosomes from parental DLD-1 cells that contain both wild-type and G13D mutant KRAS alleles and isogenically matched derivative cell lines, DKO-1 (mutant KRAS allele only) and DKs-8 (wild-type KRAS allele only). Mutant KRAS status dramatically affects the composition of the exosome proteome. Exosomes from mutant KRAS cells contain many tumor-promoting proteins, including KRAS, EGFR, SRC family kinases, and integrins. DKs-8 cells internalize DKO-1 exosomes, and, notably, DKO-1 exosomes transfer mutant KRAS to DKs-8 cells, leading to enhanced three-dimensional growth of these wild-type KRAS-expressing non-transformed cells. These results have important implications for non-cell autonomous effects of mutant KRAS, such as field effect and tumor progression.
- Subjects :
- Alleles
Cell Line, Tumor
Cell Proliferation
Chromatography, Liquid
Colonic Neoplasms genetics
Colonic Neoplasms metabolism
Exosomes metabolism
Humans
Mutation
Neoplasm Proteins metabolism
Protein Transport
Proteome metabolism
Proto-Oncogene Proteins genetics
Proto-Oncogene Proteins metabolism
Proto-Oncogene Proteins p21(ras)
Signal Transduction
Tandem Mass Spectrometry
Tumor Microenvironment
ras Proteins genetics
ras Proteins metabolism
Colonic Neoplasms chemistry
Colonic Neoplasms pathology
Exosomes chemistry
Neoplasm Invasiveness
Neoplasm Proteins chemistry
Proteome chemistry
Proto-Oncogene Proteins chemistry
ras Proteins chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1535-9484
- Volume :
- 12
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecular & cellular proteomics : MCP
- Publication Type :
- Academic Journal
- Accession number :
- 23161513
- Full Text :
- https://doi.org/10.1074/mcp.M112.022806