A new mouse study indicates that cyclophosphamide, a widely used chemotherapy drug, may enhance breast cancer cells' ability to metastasize to the lungs. It alters endothelial cells lining lung blood vessels, making it easier for cancer cells to invade and adhere. Published in the International Journal of Molecular Sciences.
Breast cancer is the most commonly diagnosed cancer worldwide and a leading cause of death among women: 685,000 deaths from 2.3 million cases in 2020. Metastasis drives most cancer fatalities, underscoring the need to understand its mechanisms.
Prior research showed chemotherapy can paradoxically boost metastasis by altering non-cancerous cells that, in turn, aid cancer cells. This study confirms it, linking higher cancer cell abundance to increased vascular wall adhesiveness.
Researchers pretreated healthy mice with cyclophosphamide (CTX), waited four days for metabolism and excretion, then injected breast cancer cells. They tracked lung accumulation.
Treated mice showed higher cancer cell concentrations in lung blood vessels three hours post-injection compared to controls.
"Our pretreatment model asks: Does chemotherapy alter normal cells to assist cancer cells? The answer is yes," says Tsonwin Hai, PhD, in a press release, calling it a "caution for chemotherapy use."
CTX initially increases blood vessel permeability by remodeling the basement membrane, enabling cancer cells to adhere.
Endothelial cells form a tight "brick wall" lining vessels, Hai explains. "Post-chemotherapy, vessels 'leak'—junctions loosen, letting cancer cells squeeze through."
The study implicates matrix metalloproteinase-2 (MMP-2), elevated after treatment. This exposes peptides RGD and YIGSR in the basement membrane, which bind cancer cell receptors, promoting adhesion.
Adhered cells evade blood flow, establishing lung footholds.
