Xeno-Cannibalism as an Exacerbation of Self-Cannibalism: A Possible Fruitful Survival Strategy for Cancer Cells

The term self-cannibalism, or autophagy, was coined to describe the ability of the cells to cannibalize their own damaged organelles or proteins. It was morphologically described as the presence of double-membraned autophagic vesicles filled with diverse cellular materials or debris inside the cells. Hence, more recently, the presence of autophagic vacuoles has been associated with cell survival, including cell senescence and cancer and appears to be activated by nutrient deprivation. The occurrence of autophagic processes can also lead, as final event, to the death of the cell. In this review we summarize the results reported in literature on a phagic process that appears to be related to self-cannibalism: the xeno-cannibalism. This was described as the ability of certain cells, e.g. metastatic cells, to cannibalize their siblings as well as cells from the immune system. Interestingly, metastatic tumor cells are also able to engulf and digest living cells, including autologous lymphocytes that should kill them, i.e. CD8+ cytotoxic lymphocytes. This can represent a formidable opportunity for metastatic cells to survive in adverse conditions such as those they encounter in their “journey” towards the target organ to establish a colony. Altogether these findings seem to suggest a pathogenetic role for cannibalic behavior in human pathology and point at this surprising cellular aggressiveness as an innovative pharmacological target in the clinical management of metastatic disease.