Overexpression of apolipoprotein A-I fused to an anti-transforming growth factor beta peptide modulates the tumorigenicity and immunogenicity of mouse colon cancer cells

Cancer Immunology, Immunotherapy : CII
José Medina-EcheverzPedro Berraondo

Abstract

Transforming growth factor beta (TGF-β) promotes tumor growth, invasion and metastasis in established tumors. In this study, we analyzed the effect of overexpressing an anti-TGF-β peptide fused to apolipoprotein A-I (ApoA-I) as a scaffold molecule. We generated and characterized stable MC38 colon carcinoma clones expressing ApoA-I fused to the anti-TGF-β peptide P144 and ApoA-I as control cells. We evaluated in vitro the gene expression profile, cell cycle and anchorage-independent growth. The in vivo tumorigenic potential and immunogenicity were analyzed inoculating the MC38 clones into C57BL/6 mice, recombination-activating gene 1 knockout mice or mice deficient in NK cells either subcutaneously or intrasplenically to generate hepatic metastases. While overexpression of ApoA-I had no effect on the parameters analyzed, ApoA-I fused to P144 markedly diminished the tumorigenic capacity and metastatic potential of MC38 in vitro and in vivo, thus generating a highly immunogenic cell line. MC38 cells transfected with ApoA-I fused to P144 triggered memory T cell responses able to eliminate the parental cell line upon re-challenge. In summary, expression of ApoA-I fused to P144 is a novel strategy to modulate TGF-β in tumor cells. Th...Continue Reading

References

Feb 13, 2003·Nucleic Acids Research·Rafael A IrizarryTerence P Speed
May 20, 2003·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Vesna IvanovićDragica Nikolić-Vukosavljević
Aug 25, 2005·The Journal of Investigative Dermatology·Begoña SantiagoJosé L Pablos
Mar 7, 2006·Lipids in Health and Disease·Jingting JiangNing Xu
Nov 1, 2007·Expert Opinion on Drug Delivery·Andras G LackoWalter J McConathy
Jun 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lucía Gil-GuerreroJuan José Lasarte
Jul 30, 2008·Cell·Joan Massagué
Feb 27, 2009·Journal of Immunotherapy·Pu LiuKarl Erik Hellström
Jun 17, 2009·International Journal of Cancer. Journal International Du Cancer·Diana LlopizPablo Sarobe
Jul 1, 2009·Molecular and Cellular Biology·Peter StorzAlex Toker
Jul 10, 2010·Nature Reviews. Immunology·Richard A FlavellPaula Licona-Limón
Mar 15, 2011·Immunotherapy·Jessica FioravantiPedro Berraondo
Mar 23, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jessica FioravantiPedro Berraondo
Apr 8, 2011·Neoplasia : an International Journal for Oncology Research·Mian M K ShahzadAnil K Sood
Nov 20, 2012·Nucleic Acids Research·J A BlakeM Westerfield
Jan 31, 2015·Nature Methods·Wolfgang HuberMartin Morgan

❮ Previous
Next ❯

Citations

Jun 1, 2017·Cell and Tissue Research·Maria VillalbaAlfonso Calvo
Mar 11, 2020·International Journal of Molecular Sciences·Lindsay M ScheetzAnna Schwendeman

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.