The metabolic cooperation between cells in solid cancer tumors

• Published in: Biochimica et biophysica acta 2014-08, Vol.1846 (1), p.216-225
• Main Authors: Icard, Philippe, Kafara, Perrine, Steyaert, Jean-Marc, Schwartz, Laurent, Lincet, Hubert
• Format: Article
• Language: English
• Subjects: Adipocytes - physiology; Animals; Autophagy; Cancer; Cell Proliferation; Human health and pathology; Humans; Immunity, Cellular; Life Sciences; Neoplasms - immunology; Neoplasms - metabolism; Neoplasms - pathology; Oxygen - metabolism; Stromal Cells - metabolism; Tumor Microenvironment - physiology; Tumoral metabolism; Tumoral microenvironment; Warburg effect; Waste products
• ISSN: 0304-419X; 0006-3002; 1879-2561
• DOI: 10.1016/j.bbcan.2014.06.002

Cancer cells cooperate with stromal cells and use their environment to promote tumor growth. Energy production depends on nutrient availability and O2 concentration. Well-oxygenated cells are highly proliferative and reorient the glucose metabolism towards biosynthesis, whereas glutamine oxidation replenishes the TCA cycle coupled with OXPHOS-ATP production. Glucose, glutamine and alanine transformations sustain nucleotide and fatty acid synthesis. In contrast, hypoxic cells slow down their proliferation, enhance glycolysis to produce ATP and reject lactate which is recycled as fuel by normoxic cells. Thus, glucose is spared for biosynthesis and/or for hypoxic cell function. Environmental cells, such as fibroblasts and adipocytes, serve as food donors for cancer cells, which reject waste products (CO2, H+, ammoniac, polyamines…) promoting EMT, invasion, angiogenesis and proliferation. This metabolic-coupling can be considered as a form of commensalism whereby non-malignant cells support the growth of cancer cells. Understanding these cellular cooperations within tumors may be a source of inspiration to develop new anti-cancer agents. •Cancer cells cooperate with stromal cells and use their environment to promote tumor growth which depends on nutrient availability and O2 concentration.•Glucose is spared for biosynthesis and/or for hypoxic cell functioning.•Environmental cells, such as fibroblasts and adipocytes, serve as food donors for cancer cells.•Lactate rejected by hypoxic cells may be recycled by normoxic cells to produce ATP by mitochondria, whereas it participates with waste products to promote EMT, invasion, and angiogenesis.