Why the Spleen is a Very Rare Site for Metastases from Epithelial Cancers

It is not known why metastases from epithelial cancers are rare in the spleen, yet common in the other major organs of the reticuloendothelial system in which, like the spleen, leucocytes display a prolonged physiological intravascular transit time. Another unresolved issue that at first seems unrelated to splenic metastases is the inconsistency between the concept of physiological granulocyte disposal through granulocyte ageing and the observation that granulocytes leave the blood in an exponential fashion (half-time 7 h), which implies random disposal. Intravascular granulocytes pass through the spleen with an exponential distribution of transit times (mean 10 min). The spleen is highly active in physiological granulocyte destruction so it is suggested that the variation in times of exposure to the splenic microenvironment converts the age-dependent granulocyte destruction observed ex vivo into the random process observed in vivo, probably through exposure to apoptosis-inducing signals. This leads to the second hypothesis, which is that cancer cells fail to survive in the spleen as a result of these pro-apoptotic signals.