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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aberrant glycosylation is a universal feature of cancer cells, and certain glycan structures are well-known markers for tumor progression. Availability and composition of sugars in the microenvironment may affect cell glycosylation. Recent studies of human breast tumor cell lines indicate their ability to take up and utilize fructose. Here we tested the hypothesis that adding fructose to culture as a carbon source induces phenotypic changes in cultured human breast tumor cells that are associated with metastatic disease. MDA-MB-468 cells were adapted to culture media in which fructose was substituted for glucose. Changes in cell surface glycan structures, expression of genes related to glycan assembly, cytoskeleton F-actin, migration, adhesion and invasion were determined. Cells cultured in fructose expressed distinct cell-surface glycans. The addition of fructose affected sialylation and fucosylation patterns. Fructose feeding also increased binding of leukoagglutinating Phaseolus vulgaris isolectin, suggesting a possible rise in expression of branching beta-1, 6 GlcNAc structures. Rhodamine-phalloidin staining revealed an altered F-actin cytoskeletal system. Fructose accelerated cellular migration and increased invasion. These data suggest that changing the carbon source of the less aggressive MDA-MB-468 cell line induced characteristics associated with more aggressive phenotypes. These data could be of fundamental importance due to the markedly increased consumption of sweeteners containing free fructose in recent years, as they suggest that the presence of fructose in nutritional microenvironment of tumor cells may negatively affect the outcome for some breast cancer patients.
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PMID:Fructose as a carbon source induces an aggressive phenotype in MDA-MB-468 breast tumor cells. 2066 30

Aerobic glycolysis plays a decisive role in cancer growth. However, its role in cancer metastasis was rarely understood. Cantharidin a natural compound from an arthropod insect cantharis exerts potent anticancer activity. Here we found cantharidin possesses significant anti-metastatic activity on breast cancer dependent on inhibition of aerobic glycolysis. Cantharidin indicates significant inhibition on migration and invasion of breast cancer cells, angiogenesis in vitro, and inhibits breast cancer cells metastasizing to liver and lung in vivo. Subsequent results revealed that cantharidin decreases the extracellular acidification rates (ECAR) but increases the oxygen consumption rates (OCR) in high metastatic cells, leading to suppression of aerobic glycolysis. This was considered to be due to inhibiting the activity of pyruvate kinase (PK) and further blocking pyruvate kinase M2 (PKM2) translocation in nucleus. Fructose-1,6-bisphosphate (FBP) and L-cysteine can significantly reverse cantharidin inhibition on breast cancer cell migration, invasion, and PKM2 translocation. Furthermore, glucose transporter 1 (GLUT1) forming a metabolic loop with PKM2 is downregulated, as well as epidermal growth factor receptor (EGFR), the regulator of the glycolytic loop. Totally, cantharidin inhibits the PKM2 nuclear translocation and breaks GLUT1/PKM2 glycolytic loop, resulting in aerobic glycolysis transformation to oxidation and subsequent reversing the metastases in breast cancer. Based on inhibiting multi signals mediated aerobic glycolysis, cantharidin could be prospectively used for prevention of metastasis in breast cancer patients.
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PMID:Breaking Glucose Transporter 1/Pyruvate Kinase M2 Glycolytic Loop Is Required for Cantharidin Inhibition of Metastasis in Highly Metastatic Breast Cancer. 3117 38

Obesity and metabolic syndrome are strongly associated with cancer, and these disorders may share a common mechanism. Recently, fructose has emerged as a driving force to develop obesity and metabolic syndrome. Thus, we assume that fructose may be the mechanism to explain why obesity and metabolic syndrome are linked with cancer. Clinical and experimental evidence showed that fructose intake was associated with cancer growth and that fructose transporters are upregulated in various malignant tumors. Interestingly, fructose metabolism can be driven under low oxygen conditions, accelerates glucose utilization, and exhibits distinct effects as compared to glucose, including production of uric acid and lactate as major byproducts. Fructose promotes the Warburg effect to preferentially downregulate mitochondrial respiration and increases aerobic glycolysis that may aid metastases that initially have low oxygen supply. In the process, uric acid may facilitate carcinogenesis by inhibiting the TCA cycle, stimulating cell proliferation by mitochondrial ROS, and blocking fatty acid oxidation. Lactate may also contribute to cancer growth by suppressing fat oxidation and inducing oncogene expression. The ability of fructose metabolism to directly stimulate the glycolytic pathway may have been protective for animals living with limited access to oxygen, but may be deleterious toward stimulating cancer growth and metastasis for humans in modern society. Blocking fructose metabolism may be a novel approach for the prevention and treatment of cancer.
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PMID:Fructose contributes to the Warburg effect for cancer growth. 3267 May 73