Fig. 2.

The intravasation process is regulated by intrinsic, microenvironmental, and mechanical factors. Intrinsic properties include genetic mutations, epigenetic changes, gene expression, and metabolic profile alterations that give cells an intravasation advantage. The cellular microenvironment consists of fibroblasts, adipocytes, pericytes, platelets, and immune cells such as macrophages and neutrophils. These cells may regulate the intravasation of cancer cells by cell‐to‐cell signaling, altering the tumor microenvironment and direct participation in the invasion process. Mechanical cues such as tissue stiffness, stress, and interstitial fluid pressure may also affect cancer cell dissemination into the circulation.