A Novel Mechanism mediated by Macrophages to Promote Peritoneal Metastasis of Ovarian Cancer

The distinct interactions among different cancer cell subclones and the tumor microenvironment are largely unknown using traditional bulk measurement.

• Observation of cellular behaviors using single-cell time-lapse microscopy reveals that in the presence of macrophages, a subset of the metastatic cells shows selective advantage of becoming polyploidy, a phenotype that could promote tumor aggressiveness and therapeutic resistance.
• The metastatic cells polarise macrophages to a tumor-associated phenotype that reinforces the polyploid phenotype.
• β-catenin signaling upregulates cancer cell surface metadherin,  which communicates through  CEACAM1  expressed by macrophages

• Polyploid cancer cells are resistant to antimitotic drugs. Targeting components of the molecular cascade identified in the study holds great therapeutic potential to disrupt polyploidization of the cancer subclones that drive metastasis.