Tumour metastasis: is tissue an issue?

Single tumour cells, or multicellular aggregates, escape into blood and lymphatic vessels from a primary solid tumour as it progresses. However, the ability of such cells to develop into metastatic outgrowths is very limited, as shown by the poor prognostic power of the presence of circulating tumour cells in cancer patients. An explanation for this low efficiency may be a temporary absence of a suitable microenvironment once the tumour cells escape from their original tissue compartment. On the basis of histopathological observations, experimental studies, and the generally accepted poor prognosis of histopathologically confirmed intravascular tumour location, we propose that the structural and functional organisation of intravascular tumour cells as a tissue has a key role in providing the optimum microenvironment for sustained malignant dissemination. Such a tissue may be a fixed or a mobile intravascular microsatellite, or an intravascular micrometastasis, which locally develops into an overt in-transit metastasis.