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Fig. 1 | Journal of Experimental & Clinical Cancer Research

Fig. 1

From: Modeling tumor cell adaptations to hypoxia in multicellular tumor spheroids

Fig. 1

Hypoxia-induced adaptations in a spheroid. Oxygen gradients within tumor spheroids lead to conditions ranging between mild physiological hypoxia to anoxia (represented here by shades of gray). This results in regionalization of tumor cell populations [91, 127]. Hypoxia develops in the spheroid core due to a combination of oxygen diffusion limitations and rapid consumption from proliferating cells [24, 33, 127]. Oxygen deprivation induces glycogen storage to facilitate subsequent metabolism and continued proliferation under more severe hypoxia [49, 62, 71]. Cycling cells in hypoxic regions experience replication stress (stalled replication forks [77] and DNA damage [71]), inducing activation of DNA damage repair (DDR) signaling. DDR allows temporary tumor cell survival and proliferation upon re-oxygenation, but after prolonged periods of severe hypoxia the replisome will disassemble [65, 84]

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