title: Microenvironmental Effects of Cell Death in Malignant Disease.
abstract: Although apoptosis is well recognized as a cell death program with clear anticancer roles, accumulating evidence linking apoptosis with tissue repair and regeneration indicates that its relationship with malignant disease is more complex than previously thought. Here we review how the responses of neighboring cells in the microenvironment of apoptotic tumor cells may contribute to the cell birth/cell death disequilibrium that provides the basis for cancerous tissue emergence and growth. We describe the bioactive properties of apoptotic cells and consider, in particular, how apoptosis of tumor cells can engender a range of responses including pro-oncogenic signals having proliferative, angiogenic, reparatory, and immunosuppressive features. Drawing on the parallels between wound healing, tissue regeneration and cancer, we propose the concept of the "onco-regenerative niche," a cell death-driven generic network of tissue repair and regenerative mechanisms that are hijacked in cancer. Finally, we consider how the responses to cell death in tumors can be targeted to provide more effective and long-lasting therapies.
authors: MRC Centre for Inflammation Research, University of Edinburgh Queen's Medical Research Institute, Edinburgh, EH16 4TJ, UK. chris.gregory@ed.ac.uk.
authors: Christopher D
authors: CD
authors: Gregory
authors: MRC Centre for Inflammation Research, University of Edinburgh Queen's Medical Research Institute, Edinburgh, EH16 4TJ, UK.
authors: Catriona A
authors: CA
authors: Ford
authors: MRC Centre for Inflammation Research, University of Edinburgh Queen's Medical Research Institute, Edinburgh, EH16 4TJ, UK.
authors: Jorine J L P
authors: JJ
authors: Voss
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001343:Autophagy / Q000502:physiology; D016923:Cell Death / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D015687:Cell Hypoxia; D006801:Humans; D007167:Immunotherapy; D008264:Macrophages / Q000502:physiology; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000502:physiology; D009369:Neoplasms / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D014411:Neoplastic Stem Cells / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D012038:Regeneration / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D055153:Stem Cell Niche; D059016:Tumor Microenvironment / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology
chemical_list: D009363:Neoplasm Proteins
keywords: Angiogenesis; Anticancer therapy; Apoptosis; Burkitt lymphoma; Cell death; Extracellular vesicle; Macrophage; Onco-regenerative niche; Starry-sky; Tumor microenvironment