Bissell began exploring the relationship between aerobic glycolysis and malignant cells more than 40 years ago. She was intrigued with a hypothesis proposed in 1924 by biochemist and future Nobel laureate Otto Heinrich Warburg, which held that increased aerobic glycolysis at the expense of respiration and higher ATP production is a cause and not a symptom of cancer. This hypothesis became controversial because many researchers could find aerobic glycolysis in normal cells. Even now the majority view holds that increased sugar uptake in cells is the result of the intense metabolic demands of tumor cells and not a cause of malignant transformation
"In a series of papers published in the early 1970s, using fibroblasts from chick embryos and their malignant counterparts, we showed that if the microenvironmental context was equalized, the rate of aerobic glycolysis was indeed higher in cancer cells under all conditions tested," Bissell says. "Clearly Warburg was correct in saying that cancer cells always had increased aerobic glycolysis; however, he was not necessarily correct in saying that the defect had to be in respiratory pathways. We found these pathways to be similarly active in normal and malignant fibroblasts, as we find also now in our breast cancer cell studies in 3D assays."
Bissell would go on to discover that the cause of increased aerobic glycolysis was a dramatic increase in glucose uptake by cancer cells, but at that time did not determine whether this increase was the cause of malignant transformation. In this new study with Onodera and Jin-Min Nam of Japan's Hokkaido University, 3D laminin-rich extracellular matrix cultures of non-malignant human breast epithelial cells from a reduction mammoplasty were compared to malignant cells derived from the study's non-malignant cells.
Bissell says this demonstration of an active role in breast cancer development for glucose uptake could only have been revealed through a 3D
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DOE/Lawrence Berkeley National Laboratory