The Mechanism of Development of Brain Metastases

Before primary tumor cells are transferred to the brain, they grow into the surrounding lymph and blood vessels. Once in the lymph vessels and, rarely, blood vessels, single tumor cells or groups of cells migrate with the current of blood or lymph. A tumor embolus must preserve its viability after it overcomes the action of the immune system or another humoral body defense system, turbulence, and circulation, and only then it “settles” in the capillary bed of the recipient organ, penetrates its parenchyma, proliferates, and forms micrometastases. Not all tumor cells that get into the lymph or blood flow will eventually provide the basis for the growth of a metastatic tumor. Thus, according to Liotta and Kohn (2003), the number of tumor microemboli that eventually form metastases is about 0.01%. The potential to metastasize depends on the number of tumor cell emboli and the specifics of interaction between the latter and homeostatic mechanisms of the host (Fidler 1997; Langley and Fidler 2013).