CSIG-04. BMP4 INDUCTION OF A SENESCENCE-LIKE PHENOTYPE IN HUMAN GLIOBLASTOMA CELLS IS PARTIALLY DEPENDENT ON P21

Abstract Bone morphogenetic protein 4 (BMP4) was initially suggested as a potential differentiation-inducing factor to be used in the therapy of glioblastoma. We and others have however demonstrated that response is reversible, variable among patient samples, heterogeneous within same cell line. To deepen our knowledge on how BMP4 affects different types glioblastoma cells, we treated phenotypically clones from tumor—a multitherapy-sensitive/proneural-like (SENS/PN) clone multitherapy-resistant/mesenchymal-like (RES/MES) clone—with BMP4. In SENS/PN clone, turned mesenchymal-related gene program, whereas this less prominent RES/MES clone. Untreated cells were smaller than but both responded by size enlargement. Increase has been precede senescence; young are old eventually enter replicative senescence. induced senescence-like phenotype subpopulation induction senescence-associated (SA)-β-gal, p21 up-regulation, lamin B1 down-regulation, well increased lysosomal mass granularity. This more pronounced it dependent canonical SMAD signaling. Senolytic treatment ablated SA-β-gal positive reduced level at population level. Targeted deletion abolished BMP4-induced increase growth, while down-regulation remained, demonstrating signaling crucial for one part senescence currently further investigating connection between size, mesenchymality hypothesize large mesenchymal-like closer proneural culture. A combination senescence-induction senolytic may open opportunities target therapy-resistant cells.