Autophagy and the tumor microenvironment

Daolin Tang, Michael T. Lotze

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations

Abstract

Malignant cells do not act as separate entities; they exist in the context of an emergent microenvironment that they create in concert with the host over several years of intimate interaction. The tumor microenvironment (TME) is composed of inflammatory/immune cells, endothelial cells, fibroblasts, cytokines, chemokines, growth factors and the extracellular matrix. The TME has been implicated in the regulation of tumor initiation and progression, determining metastatic potential, and impacting the response to therapy. The TME is highly dynamic and contains subpopulations of cancer cells with temporally varying gradients of cellular metabolism, O 2 content, pH, genomic stability and a propensity for aggressive behavior. The stressors present within the TME, include hypoxia, low nutrient availability, immune infiltrates, inflammatory factors and unscheduled cell death associated with release of endogenous damage associated molecular pattern (DAMP) molecules. DAMPs, including the chromatin-binding protein high mobility group box 1 (HMGB1), alert the host of tissue damage or injury by triggering immune responses and activating stress mechanisms such as autophagy through their interaction with pattern recognition receptors. Autophagy, a conserved lysosomal degradation pathway, is a cell maintenance program that is operative at basal levels in all cells, extinguishing during traversion of the cell cycle. It is invoked at higher levels as a survival mechanism in response to environmental and cellular stress. The role of autophagy in cancer including the TME is complex and may differ depending on tumor type or context. In this chapter, recent advances in our understanding of autophagic molecular mechanisms and functions in the TME are reviewed.

Original languageEnglish (US)
Title of host publicationAutophagy and Cancer
PublisherSpringer New York
Pages167-189
Number of pages23
ISBN (Electronic)9781461465614
ISBN (Print)9781461465607
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

Keywords

  • Apoptosis
  • Autophagy
  • Cytokine
  • DAMP
  • Fibroblast
  • HMGB1
  • Hypoxia
  • Immune cells
  • Necrosis
  • NF-κB
  • RAGE
  • STAT3
  • Tumor microenvironment

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Autophagy and the tumor microenvironment'. Together they form a unique fingerprint.

Cite this