Knocking down galectin 1 in human hs683 glioblastoma cells impairs both angiogenesis and endoplasmic reticulum stress responses.
Galectin (Gal) 1 is a hypoxia-regulated proangiogenic factor that also directly participates in glioblastoma cell migration. To determine how Gal-1 exerts its proangiogenic effects, we investigated Gal-1 signaling in the human Hs683 glioblastoma cell line. Galectin 1 signals through the endoplasmic reticulum transmembrane kinase/ribonuclease inositol-requiring 1alpha, which regulates the expression of oxygen-regulated protein 150. Oxygen-regulated protein 150 controls vascular endothelial growth factor maturation. Galectin 1 also modulates the expression of 7 other hypoxia-related genes (i.e. CTGF, ATF3, PPP1R15A, HSPA5, TRA1, and CYR61) that are implicated in angiogenesis. Decreasing Gal-1 expression in Hs683 orthotopic xenografts in mouse brains by siRNA administration impaired endoplasmic reticulum stress and enhanced the therapeutic benefits of the proautophagic drug temozolomide. These results suggest that decreasing Gal-1 expression (e.g. through brain delivery of nonviral infusions of anti-Gal-1 siRNA in patients) can represent an additional therapeutic strategy for glioblastoma.
Le Mercier
Marie
M
Laboratory of Toxicology, Institute of Pharmacy, Free University of Brussels, Brussels, Belgium.
Mathieu
Véronique
V
Haibe-Kains
Benjamin
B
Bontempi
Gianluca
G
Mijatovic
Tatjana
T
Decaestecker
Christine
C
Kiss
Robert
R
Lefranc
Florence
F
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D004722:Endoribonucleases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005260:Female; D037483:Galectin 1 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D020868:Gene Silencing / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D050956:HSP40 Heat-Shock Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins; D006801:Humans; D008565:Membrane Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018832:Molecular Chaperones / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D018384:Oxidative Stress / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference / Q000187:drug effects / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000235:genetics; D000077204:Temozolomide; D014183:Transplantation, Heterologous
D018906:Antineoplastic Agents, Alkylating; C478021:DNAJB9 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; D037483:Galectin 1; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C000717247:HSPA5 protein, human; C000717248:Hspa5 protein, mouse; D008565:Membrane Proteins; D018832:Molecular Chaperones; D011506:Proteins; D034741:RNA, Small Interfering; C050087:oxygen-regulated proteins; D003606:Dacarbazine; C403982:ERN2 protein, human; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases; D000077204:Temozolomide