Open AccessLoss of Sparc in p 53 ‐null Astrocytes Promotes Macrophage Activation and Phagocytosis Resulting in Decreased Tumor Size and Tumor Cell Survival
Author(s) -
Thomas Stacey L.,
Schultz Chad R.,
Mouzon Ezekiell,
Golembieski William A.,
Naili Reima El,
Radakrishnan Archanna,
Lemke Nancy,
Poisson Laila M.,
Gutiérrez Jorge A.,
Cottingham Sandra,
Rempel Sandra A.
Publication year - 2015
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12161
Subject(s) - phagocytosis , macrophage , glioblastoma , cancer research , cell survival , microbiology and biotechnology , biology , immunology , medicine , chemistry , cell culture , in vitro , genetics
Both the induction of SPARC expression and the loss of the p53 tumor suppressor gene are changes that occur early in glioma development. Both SPARC and p53 regulate glioma cell survival by inverse effects on apoptotic signaling. Therefore, during glioma formation, the upregulation of SPARC may cooperate with the loss of p53 to enhance cell survival. This study determined whether the loss of Sparc in astrocytes that are null for p53 would result in reduced cell survival and tumor formation and increased tumor immunogenicity in an in vivo xenograft brain tumor model. In vitro , the loss of S parc in p53 ‐null astrocytes resulted in an increase in cell proliferation, but a loss of tumorigenicity. At 7 days after intracranial implantation, Sparc ‐null tumors had decreased tumor cell survival, proliferation and reduced tumor size. The loss of Sparc promoted microglia/macrophage activation and phagocytosis of tumor cells. Our results indicate that the loss of p53 by deletion/mutation in the early stages of glioma formation may cooperate with the induction of SPARC to potentiate cancer cell survival and escape from immune surveillance.