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Treating the Intestine with Oral ApoA-I Mimetic Tg6F Reduces Tumor Burden in Mouse Models of Metastatic Lung Cancer.
Chattopadhyay, Arnab; Yang, Xinying; Mukherjee, Pallavi; Sulaiman, Dawoud; Fogelman, Hannah R; Grijalva, Victor; Dubinett, Steven; Wasler, Tonya C; Paul, Manash K; Salehi-Rad, Ramin; Mack, Julia J; Iruela-Arispe, M Luisa; Navab, Mohamad; Fogelman, Alan M; Reddy, Srinivasa T.
Afiliación
  • Chattopadhyay A; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095-1736, USA.
  • Yang X; Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095-1736, USA.
  • Mukherjee P; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095-1736, USA.
  • Sulaiman D; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095-1736, USA.
  • Fogelman HR; Molecular Toxicology Interdepartmental Degree Program, Fielding School of Public Health, University of California, Los Angeles, CA, 90095-1736, USA.
  • Grijalva V; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095-1736, USA.
  • Dubinett S; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095-1736, USA.
  • Wasler TC; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095-1736, USA.
  • Paul MK; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095-1736, USA.
  • Salehi-Rad R; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095-1736, USA.
  • Mack JJ; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095-1736, USA.
  • Iruela-Arispe ML; Department of Molecular, Cell and Developmental Biology, College of Letters and Science, University of California, Los Angeles, CA, 90095-1736, USA.
  • Navab M; Department of Molecular, Cell and Developmental Biology, College of Letters and Science, University of California, Los Angeles, CA, 90095-1736, USA.
  • Fogelman AM; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095-1736, USA.
  • Reddy ST; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095-1736, USA.
Sci Rep ; 8(1): 9032, 2018 06 13.
Article en En | MEDLINE | ID: mdl-29899427
Having demonstrated that apolipoprotein A-I (apoA-I) mimetic peptides ameliorate cancer in mouse models, we sought to determine the mechanism for the anti-tumorigenic function of these peptides. CT-26 cells (colon cancer cells that implant and grow into tumors in the lungs) were injected into wild-type BALB/c mice. The day after injection, mice were either continued on chow or switched to chow containing 0.06% of a concentrate of transgenic tomatoes expressing the apoA-I mimetic peptide 6F (Tg6F). After four weeks, the number of lung tumors was significantly lower in Tg6F-fed mice. Gene expression array analyses of jejunum and lung identified Notch pathway genes significantly upregulated, whereas osteopontin (Spp1) was significantly downregulated by Tg6F in both jejunum and lung. In jejunum, Tg6F increased protein levels for Notch1, Notch2, Dll1, and Dll4. In lung, Tg6F increased protein levels for Notch1 and Dll4 and decreased Spp1. Tg6F reduced oxidized phospholipid levels (E06 immunoreactivity) and reduced 25-hydroxycholesterol (25-OHC) levels, which are known to inhibit Notch1 and induce Spp1, respectively. Notch pathway promotes anti-tumorigenic patrolling monocytes, while Spp1 facilitates pro-tumorigenic myeloid derived suppressor cells (MDSCs) formation. Tg6F-fed mice had higher numbers of patrolling monocytes in jejunum and in lung (p < 0.02), and lower plasma levels of Spp1 with reduced numbers of MDSCs in jejunum and in lung (p < 0.03). We conclude that Tg6F alters levels of specific oxidized lipids and 25-OHC to modulate Notch pathways and Spp1, which alter small intestine immune cells, leading to similar changes in lung that reduce tumor burden.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos / Apolipoproteína A-I / Carga Tumoral / Neoplasias Pulmonares / Neoplasias Experimentales Límite: Animals Idioma: En Revista: Sci Rep Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos / Apolipoproteína A-I / Carga Tumoral / Neoplasias Pulmonares / Neoplasias Experimentales Límite: Animals Idioma: En Revista: Sci Rep Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido