Oncoprotein signaling mediates tumor-specific inflammation and enhances tumor progression - PubMed (original) (raw)
Oncoprotein signaling mediates tumor-specific inflammation and enhances tumor progression
Jeff S Pufnock et al. J Immunol. 2009.
Abstract
The RET/PTC3 (RP3) fusion protein is an oncogene expressed during the development of thyroid cancer and in thyroid epithelial cells of patients with Hashimoto's thyroiditis. RP3 has two immunological properties: 1) it encodes a chimeric protein including peptides that may be targets of antitumor immune responses and 2) it is a tyrosine kinase that can activate NF-kappaB transcriptional programs, induce secretion of proinflammatory mediators, and stimulate innate immunity. To distinguish the antigenic properties of the RP3 oncoprotein from its signaling function, a transplantable tumor system was developed. Tumors expressing the functional, but not mutant, form of RP3 show enhanced infiltration of CD8(+) lymphocytes, myeloid-derived CD11b(+)Gr1(+) cells, and enhanced growth in immunocompetent mice. In contrast, RP3 signaling mutant-expressing tumors maintained enhanced infiltration of CD8(+) lymphocytes did not enhance recruitment of CD11b(+)Gr1(+) cells and showed a decreased tumor incidence. These results implicate a role for RP3 function in enhancing a tumor-suppressive innate inflammatory response. These experiments support a mechanism whereby oncogenes can directly recruit and activate innate and adaptive immune cells, resulting in enhanced tumor progression.
Similar articles
- Proinflammatory mediators and genetic background in oncogene mediated tumor progression.
Russell JP, Engiles JB, Rothstein JL. Russell JP, et al. J Immunol. 2004 Apr 1;172(7):4059-67. doi: 10.4049/jimmunol.172.7.4059. J Immunol. 2004. PMID: 15034017 - A thyroid tumor-specific antigen formed by the fusion of two self proteins.
Powell DJ Jr, Eisenlohr LC, Rothstein JL. Powell DJ Jr, et al. J Immunol. 2003 Jan 15;170(2):861-9. doi: 10.4049/jimmunol.170.2.861. J Immunol. 2003. PMID: 12517951 - Tyrosine kinase oncoprotein, RET/PTC3, induces the secretion of myeloid growth and chemotactic factors.
Russell JP, Shinohara S, Melillo RM, Castellone MD, Santoro M, Rothstein JL. Russell JP, et al. Oncogene. 2003 Jul 17;22(29):4569-77. doi: 10.1038/sj.onc.1206759. Oncogene. 2003. PMID: 12881713 - The Yin-Yang of tumor-associated macrophages in neoplastic progression and immune surveillance.
Allavena P, Sica A, Garlanda C, Mantovani A. Allavena P, et al. Immunol Rev. 2008 Apr;222:155-61. doi: 10.1111/j.1600-065X.2008.00607.x. Immunol Rev. 2008. PMID: 18364000 Review. - Dysregulated RET signaling in thyroid cancer.
Castellone MD, Santoro M. Castellone MD, et al. Endocrinol Metab Clin North Am. 2008 Jun;37(2):363-74, viii. doi: 10.1016/j.ecl.2008.02.006. Endocrinol Metab Clin North Am. 2008. PMID: 18502331 Review.
Cited by
- Rethinking the chemokine cascade in brain metastasis: Preventive and therapeutic implications.
Maurya SK, Khan P, Rehman AU, Kanchan RK, Perumal N, Mahapatra S, Chand HS, Santamaria-Barria JA, Batra SK, Nasser MW. Maurya SK, et al. Semin Cancer Biol. 2022 Nov;86(Pt 3):914-930. doi: 10.1016/j.semcancer.2021.12.009. Epub 2021 Dec 27. Semin Cancer Biol. 2022. PMID: 34968667 Free PMC article. Review. - CCL2/CCR2 signaling in cancer pathogenesis.
Hao Q, Vadgama JV, Wang P. Hao Q, et al. Cell Commun Signal. 2020 May 29;18(1):82. doi: 10.1186/s12964-020-00589-8. Cell Commun Signal. 2020. PMID: 32471499 Free PMC article. Review. - Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictors of tumor response in hepatocellular carcinoma after DEB-TACE.
Schobert IT, Savic LJ, Chapiro J, Bousabarah K, Chen E, Laage-Gaupp F, Tefera J, Nezami N, Lin M, Pollak J, Schlachter T. Schobert IT, et al. Eur Radiol. 2020 Oct;30(10):5663-5673. doi: 10.1007/s00330-020-06931-5. Epub 2020 May 19. Eur Radiol. 2020. PMID: 32424595 Free PMC article. - Innate and adaptive immune cells in the tumor microenvironment.
Gajewski TF, Schreiber H, Fu YX. Gajewski TF, et al. Nat Immunol. 2013 Oct;14(10):1014-22. doi: 10.1038/ni.2703. Nat Immunol. 2013. PMID: 24048123 Free PMC article. Review. - Inflammation in thyroid oncogenesis.
Liotti F, Visciano C, Melillo RM. Liotti F, et al. Am J Cancer Res. 2012;2(3):286-97. Epub 2012 Apr 21. Am J Cancer Res. 2012. PMID: 22679559 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials