Periostin (POSTN) Regulates Tumor Resistance to Antiangiogenic Therapy in Glioma Models.
Periostin (POSTN) interacts with multiple integrins to coordinate a variety of cellular processes, including epithelial-to-mesenchymal transition (EMT) and cell migration. In our previous study, anti-VEGF-A therapy was associated with resistance and EMT. This study sought to determine the role of POSTN in the resistance of glioma stem cells (GSC) to antiangiogenic therapy. In mouse xenograft models of human glioma, POSTN expression was associated with acquired resistance to anti-VEGF-A therapy and had a synergistic effect with bevacizumab in prolonging survival and decreasing tumor volume. Resistance to anti-VEGF-A therapy regulated by POSTN was associated with increased expression of TGFβ1 and hypoxia-inducible factor-1α (HIF1α) in GSCs. At the molecular level, POSTN regulated invasion and expression of EMT (caveolin-1) and angiogenesis-related genes (HIF1α and VEGF-A) through activation of STAT3. Moreover, recombinant POSTN increased GSC invasion. Collectively, our findings suggest that POSTN plays an important role in glioma invasion and resistance to antiangiogenic therapy. Mol Cancer Ther; 15(9); 2187-97. ©2016 AACR.
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Soon Young
SY
Park
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Yuji
Y
Piao
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Kang Jin
KJ
Jeong
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Jianwen
J
Dong
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. jdegroot@mdanderson.org.
John F
JF
de Groot
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; C512835:POSTN protein, human; D016212:Transforming Growth Factor beta