Scientists at The Wistar Institute discovered that a common sugar released by chemotherapy-surviving cancer cells acts as a chemical signal encouraging nearby tumors to break free and spread.
Most patients with ovarian cancer receive platinum-based chemotherapy to damage cancer cell DNA and halt reproduction. Although initial responses are common, the disease frequently returns and spreads throughout the abdominal cavity. Metastasis accounts for approximately 90% of ovarian cancer deaths, according to findings published in Nature Aging.
Researchers developed experiments separating surviving cancer cells from their secreted molecules. They found these released substances alone significantly drove cancer spread in preclinical models. ScienceDaily reported that Aidan Cole, a postdoctoral fellow, noted these cells remain biologically active despite no longer dividing.
“Some cancer cells that survive chemotherapy aren’t dividing anymore, but they’re still biologically active,” remarked Aidan Cole, who works as a postdoctoral researcher within Katherine Aird’s laboratory at The Wistar Institute and serves as the study’s primary author. “Instead, they continue to release molecules that send signals to nearby cells. Our study is among the first to show that a nutrient — in this case, fructose — can act as one of those signals.”
Fructose Promotes Cancer Cell Migration
Investigators identified the unexpected signaling molecule as fructose, a natural sugar found in fruit, honey, table sugar, and high fructose corn syrup. Rather than acting strictly as an energy source, the secreted sugar prompts neighboring cancer cells to increase their migratory capacity. High dietary fructose consumption alone promoted similar spreading signals in preclinical experiments without prior chemotherapy exposure.
Dietary fructose accounts for roughly 8% to 20% of daily caloric intake for certain individuals in the United States. Researchers emphasize that these findings do not establish that eating sugar directly causes human cancer to spread. Additional clinical studies are required before medical professionals can issue specific dietary guidelines based on this metabolic pathway.
Inside the targeted cells, fructose suppresses cholesterol synthesis. Cholesterol normally maintains cell membranes and the biological glue connecting neighboring cells. When cholesterol drops, these intercellular junctions weaken, allowing malignant cells to detach and migrate.
Statins Weaken Connections Between Cancer Cells
The cholesterol mechanism prompted scientists to examine statins, widely prescribed medications utilized by roughly 39 million Americans to lower cardiovascular risks. Preclinical tests showed statins alone similarly weakened connections between cancer cells. Katherine Aird, Ph.D., who holds positions as a professor and co-leads the Molecular and Cellular Oncogenesis Program located inside the Ellen and Ronald Caplan Cancer Center at The Wistar Institute, discussed the implications for postmenopausal patients.
“We haven’t tested this effect in patients yet, but it raises questions about combining cholesterol-lowering drugs with chemotherapy, especially since ovarian cancer is most common in postmenopausal women who are often already on statins,” noted the study’s senior author, Katherine Aird, Ph.D., who is a professor and co-leader of the Molecular and Cellular Oncogenesis Program at The Wistar Institute’s Ellen and Ronald Caplan Cancer Center.
Investigators suspect this mechanism is not unique to ovarian tumors. Aird said that other cancers spreading within the torso, including pancreatic, colon, and liver cancers, might operate through parallel pathways. The research team has initiated new experiments to test these cellular behaviors across additional gastrointestinal and abdominal malignancies.
Fructose Secretion Weakens Tumor Cell Bonds
- Chemotherapy Survivers: Cancer cells surviving chemotherapy can secrete fructose, signaling nearby tumors to break apart and metastasize.
- Cellular Adhesion: Fructose reduces cellular cholesterol, weakening the physical bonds holding tumor cells together.
- Medication Questions: While statins weaken these cell bonds in preclinical models, researchers stress patients should not stop taking prescribed cholesterol medications.
| Biological Factor | Observed Effect in Preclinical Models | Clinical Relevance |
|---|---|---|
| Fructose Secretion | Acts as a chemical messenger driving tumor cell detachment | Under investigation; dietary impact unproven in human trials |
| Cholesterol Suppression | Weakens cellular membranes and inter-cell bonds | Links metabolic byproducts directly to metastatic potential |
| Statin Administration | Mimics cholesterol reduction, easing cell separation | Requires caution; does not replace current cardiovascular guidelines |
References
- Nature Aging: Fructose acts as a paracrine signal promoting tumor dissemination after chemotherapy
- The Wistar Institute: Research announcements regarding metabolic signaling in aggressive ovarian cancer
- News-Medical.net: Coverage of cellular pathways influencing cancer metastasis
