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Fig. 1 | Cancer Cell International

Fig. 1

From: The role of hypoxia in the tumor microenvironment and development of cancer stem cell: a novel approach to developing treatment

Fig. 1

The diagram displays the responses to reduced oxygenation within the tumor microenvironment. Hypoxia promotes tumor invasion, metastasis and resistance through several ways. a Hypoxia induces detachment of tumor cells by weakening the connections between cells and their extracellular matrix supporting them, and promotes dissemination of tumor cells to the various organs of the body. Thereby hypoxia triggers the metastatic spread of tumor. b Hypoxia stimulates angiogenesis, and provides more opportunity for detached tumor cell to inter into the circulation and migrate via the newly formed vessels. Thereby hypoxia enhances invasive and metastatic spread of solid tumors to another region. c Hypoxia induces EMT, in which tumor cells detach, lose the epithelial feature, acquire a mesenchymal phenotype and display the stemness properties including loss of differentiation, tumorigenesis and aggressiveness. EMT extensively contributes to promoting of tumor cell invasion and migration. d Hypoxia up-regulates CAFs that produce the excessive altered ECM, which supports tumor growth and metastasis. e Tumor hypoxia promotes secretion of cytokines and chemokines that recruit pro-tumor immune cell and suppress anti-tumor response of various types of immune cells. f In response to hypoxia, tumor cells exploit a number of mechanisms including, extrusion of cytotoxic drug by ABC-transporters, exhibiting quiescent state, acquiring metabolic adaptations and displaying stemness features, which can contribute in chemo-, radio- therapy failure. g Hypoxia acts as a niche condition, to accumulate the CSCs enhancing tumorigenesis and resistance. EMT epithelial to mesenchymal transition, CAF cancer-associated fibroblast, ECM extracellular matrix, MDSCs myeloid-derived suppressor cells, TAM tumor-associated macrophage, TAN tumor-associated neutrophil, Treg regulatory T lymphocyte, NK cell natural killer cell, CSC cancer stem cell

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