Tumor Cell Migration May Be an Inherent “Foraging” Behavior

ABSTRACT Background Tumor metastasis is a leading cause of cancer‐related death, fundamentally dependent on cell motility—a conserved behavior enabling cells to move directionally in response to environmental signals. Eco‐oncology posits that tumors function as cellular ecosystems; however, the individual migration behavior of tumor cells, particularly their potential “foraging” activities, remains poorly understood. Our study observes the biological behavior of independent tumor cells during migration to understand how they utilize available resources to achieve their survival goals, and whether they compete with and interact with “companions” that are also migrating. Methods We used live‐cell dynamic imaging analysis to observe the migration of individual CT26 and A549 tumor cells over time. Cells were cultured at low density, and a subset of CT26 cells was labeled with enhanced green fluorescent protein (EGFP) for visualization. Cell interactions and motility were recorded every 10 min, and cell contact was detected using Wright staining. Results Tumor cells migrated by extending pseudopodia‐like membrane processes, simultaneously undergoing cell division and proliferation. Cells actively migrated to the vicinity of dead cells or cell debris, capturing and absorbing these substances within minutes. Frequent intercellular contact occurred, with stronger cells absorbing the cytoplasm of weaker cells, ultimately leaving only nuclear remnants. Cells also exhibited the ability to cleave and absorb debris from adjacent cellular structures. Conclusions Individual tumor cells exhibit intrinsic, active foraging‐like behavior during migration, including acquiring nutrients from dead cells and competing with neighboring surviving cells. Tumor cell motility should be viewed not only as a mechanistic process but also as a resource‐seeking survival strategy.