title: Blebbishields, the emergency program for cancer stem cells: sphere formation and tumorigenesis after apoptosis.
abstract: Caspases mediate apoptosis and have also been implicated in stem-cell biology. How caspases are linked to stem-cell biology is not known. Here, we show that the apoptotic blebs of cancer cells fuse together to form novel structures called 'blebbishields'. Blebbishields form spheres by fusion. Both blebbishield formation and sphere formation involve active caspases and N-linked glycosylation. Sphere formation is enhanced by acidic pH and is counteracted by inhibitors of proton pump, caspases, and cholesterol. The blebbishields from VEGFR2(High) cells are capable of enhanced sphere formation. Blebbishields express transiently downregulated stem-cell markers and the sphere-forming blebbishield-derived cells are tumorigenic. Our study demonstrates that the cancer stem cells can survive after apoptosis by blebbishield formation and subsequent sphere formation.
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: G G
authors.initials: GG
authors.lastname: Jinesh
authors.forename: W
authors.initials: W
authors.lastname: Choi
authors.forename: J B
authors.initials: JB
authors.lastname: Shah
authors.forename: E K
authors.initials: EK
authors.lastname: Lee
authors.forename: D L
authors.initials: DL
authors.lastname: Willis
authors.forename: A M
authors.initials: AM
authors.lastname: Kamat
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D061945:Caspase Inhibitors / Q000494:pharmacology; D020169:Caspases / Q000737:chemistry / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D015536:Down-Regulation; D006031:Glycosylation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism*; D054328:Proton Pump Inhibitors / Q000494:pharmacology; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction; D018874:Spheroids, Cellular / Q000166:cytology*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D061945:Caspase Inhibitors; D054328:Proton Pump Inhibitors; D040301:Vascular Endothelial Growth Factor Receptor-2; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D020169:Caspases