Fig. 1.

The tumor microenvironment (TME) and the cascade of breast cancer metastasis. Tumor dissemination is initiated by the uncontrolled growth of the tumor and the formation of angiogenesis, a process where new blood vessels are formed from the preexisting ones. These vessels are employed to provide nutrients and oxygen to the tumor. Next, metastatic cancer cells invade the surrounding TME and migrate directionally towards the microvasculature to invade it in a process known as intravasation. Then, these tumor cells travel through the blood vessels as circulating tumor cells (CTCs) to invade distant organs. Many of these CTCs are destroyed or damaged during the circulation due to their inability to transit through the capillaries. A few undamaged cells may extravasate and invade the parenchyma of a foreign tissue (e.g., liver, brain, bone, or lung). At the invading stage, cancer cells start proliferating forming a secondary tumor site. Therein, multiple immune cells, such as macrophages, natural killer cells, T lymphocytes and dendritic cells, reside in the tumor niche (Created using Biorender.com).