Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice.

By P. Sonveaux, F. Végran, Thies Schroeder, M. Wergin, J. Verrax, Z. Rabbani, Christophe J. De Saedeleer, Kelly M. Kennedy, C. Diepart, B. Jordan and 5 more. Journal of Clinical Investigation, 2008

1,679 citations recorded by the source corpus.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/71010ab09ca566a4d022f03056ac986f77d0b368

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Citations in the corpus

Targeting Metabolism for Cancer Therapy (2017, background): “…that lactate produced by cancer-associated fibroblasts can enter the TCA cycle of cancer cells (Bonuccelli et al., 2014; Witkiewicz et al., 2012), and lactate produced in hypoxic regions of a tumor can fuel respiration in welloxygenated tumor cells (Kennedy et al., 2013; Sonveaux et al., 2008).”
The Warburg effect: essential part of metabolic reprogramming and central contributor to cancer progression (2019, background): “Upon export through MTC4-symporters into the extracellular space and accumulation in the TME, lactate – by contrast – can be imported by normoxic cancer (and stromal) cells via MTC1-symporters and utilized to fuel OXPHOS, thus sparing the uptake of glucose which is – as described above – avidly cons”
Metabolic Interactions in the Tumor Microenvironment (2017, background): “This process is supported by well oxygenated cancer cells, which consume lactate discarded by the hypoxic cancer cells to fuel mitochondrial metabolism [43].”
The Acidic Tumor Microenvironment as a Driver of Cancer. (2019, background): “in different microenvironmental conditions (68) (see the section titled Stromal Cell Adaptations and Cellular Interactions in the Tumor Microenvironment).”
The Science and Translation of Lactate Shuttle Theory. (2018, background): “…(Fantin et al., 2006; Shim et al., 1997), while approaches to target MCTs, thereby blocking lactate transport across cancer cell membranes, have shown effectiveness in decreasing both angiogenesis and cell migration (Doherty et al., 2014; Draoui and Feron, 2011; Sonveaux et al., 2012).”
Lactate metabolism in human lung tumors (2017, positive): “Blocking lactate uptake with an MCT1 inhibitor reduces respiration and promotes glycolysis in some cancer cell lines and suppresses xenograft growth in mice (Pavlides et al., 2009; Sonveaux et al., 2008).”
Metabolic Instruction of Immunity (2017, positive): “Lesser-perfused regions of the lung tumors were associated with higher glucose metabolism whereas higher-perfused regions could utilize circulating lactate, transported through monocarboxylate transporter 1 (MCT1), as an alternative TCA cycle substrate (Sonveaux et al., 2008).”
Systems analysis of intracellular pH vulnerabilities for cancer therapy (2018, methodology): “However, the strategy fails to kill triple negative MDA-MB-231 breast cancer cells, where a suf ﬁ ciently low pHi was unattainable (Supplementary Figure 15), presumably due to the elevated expression of the MCT4 transporter that is resistant to the effects of the selective MCT1/ 2 inhibitor 35,36 .”
HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. (2013, positive): “Disruption of this metabolic symbiosis by treatment of tumor-bearing mice with α -cyano-4-hy- droxycinnamate inhibited MCT1 activity such that aerobic cells were forced to take up glucose rather than lactate, leading to glucose depletion and the death of hypoxic cancer cells (53).”
Links between metabolism and cancer. (2012, background): “In this regard, cancer cells and stromal cells can symbiotically recycle and maximize the use of nutrients (Sonveaux et al. 2008).”
Understanding the intersections between metabolism and cancer biology (2017, positive): “A similar symbiotic relationship may exist within tumors, where some cells ferment glucose to lactate, which is then used as a respiratory substrate for other cells (Sonveaux et al., 2008).”
The updated landscape of tumor microenvironment and drug repurposing (2020, background): “Sonveaux et al.(101) demonstrated a phenomenon called “glycolytic switch” and “metabolic symbiosis”, and stated that oxidative cancer cells prefer utilizing lactate rather than glucose, in which MCT1 mediates a lactate exchange in tumors.”
Adipose tissue and adipocytes supports tumorigenesis and metastasis (2013, positive): “They named this process, metabolic symbiosis and further showed that blocking the monocarboxylate transporter causes death of the hypoxic region of the tumor [79].”
Targeting metabolic transformation for cancer therapy (2010, background): “Interestingly, a recent report suggested that there is a swapping of lactate between oxygenated and hypoxic cells in tumours, much like that found in muscl”
Q's next: The diverse functions of glutamine in metabolism, cell biology and cancer (2009, background): “Sonveaux et al. (2008) identified the cell surface monocarboxylate transporter type 1 as the enabler of such a metabolic symbiosis in xenografts.”
Distinct metabolic flow enables large-scale purification of mouse and human pluripotent stem cell-derived cardiomyocytes. (2013, methodology): “For investigation of the significance of MCT1 expression for lactate uptake in cardiomyocytes, the cells were treated with MCT1 inhibitor a-cyano-4-hydroxycinnamate (a-CHC) (Sonveaux et al., 2008) under glucose-free and lactate-rich conditions.”