Decreasing Galectin-1 Expression in Human Hs683 Glioblastoma Cells Impairs their Response to Endoplasmic Reticulum Stress 

Le Mercier M, Camby I, Mathieu V, Dumont P, De Neve N, Roland I, Haibe-Kains B, Bontempi G, Mijatovic T, Kondo Y, Decaestecker C, Kiss R, Lefranc F

Glioblastomas (GBMs) are resistant to apoptosis, but not to autophagy, a fact that can, at least partly, explain the therapeutic benefits of the pro-autophagic drug temozolomide in the treatment of GBM patients. Galectin-1 is a potent modulator of GBM cell migration and a close partner of Ras, whose importance as a signaling molecule in the case of GBMs has already been highlighted. The data in the present study show that the depletion by anti-galectin-1 siRNA of galectin-1 expression in human Hs683 GBM cells does not induce apoptotic or autophagic features. In contrast, this galectin-1 depletion decreases the levels of expression of several genes involved in the response to the endoplasmic reticulum (ER) stress (ERS), and including DUSP5, HERP, DNAJB9/MDG1/Erdj4 and ORP150/HYOU1, the latter of which modulates angiogenesis via the processing of VEGF. The depletion of galectin-1 expression in Hs683 tumor cells leads to sustained decreases in VEGF expression, with severe in vivo impairments of angiogenesis in Hs683 orthotopic xenografts. The in vivo delivery of a non-viral infusion of anti-galectin-1 siRNA into the ventricular system of the brains of adult mice orthotopically grafted with Hs683 GBM cells increases the anti-tumor effects of temozolomide. This novel facet of galectin-1 involvement in glioblastoma biology may be amenable to therapeutic manipulation.