Oncosomes – large and small: what are they, where they came from?

Oncosomes Á large and small: what are they, where they came from? Dear Editor, Terminology matters. After all this is the basis of the formal code that allows investigators to communicate, compare notes and use computational tools to access molecular databases. If the same term is assigned different or inconsistent meanings, or different terms are used to describe the same entity, communications degenerate. This is why occasional debate on what specific terms mean, where they came from, and what is their best use is a healthy exercise. Few scientific communities experienced this problem more acutely than those of us who work on what is now collectively described as extracellular vesicles (EVs). The underlying biological complexity, technical considerations , historical reasons and cultures of different parental research fields have stimulated semantic creativity to produce a mind numbing plethora of descriptors, including others, the meaning of which is only recently being more rigorously considered (1Á3). The case in point are EVs known as ''oncosomes.'' At the time of this writing, there were at least 26 PubMed citations and a handful of authoritative review articles, in which the term ''oncosomes'' has been used (including as key word) to highlight different aspects of EV release by cancer cells (4Á7). In spite of its intuitive usefulness and convenient ''ring,'' this term is often applied in ways that have little to do with its intended meaning, circumstances under which it has been coined in our respective laboratories , ontologic efficiency or any consensus in the field. Therefore, some context may be useful in putting things in perspective towards establishing meaningful definitions. In 2008, we described the first piece of experimental evidence that the oncogenic form (variant III) of the epidermal growth factor receptor (EGFR), EGFRvIII, which is relatively specific to human glioblastoma (GBM), is released from brain tumour cells as cargo of EVs that range between 100 and 400 nm in diameter and carry phosphatidylserine on their surfaces (8). While the biogen-esis of these EVs was initially unknown, this observation signified the ability of EVs to mediate the extracellular exit of structurally and functionally abnormal, mutant and potentially transforming macromolecules (oncogenes). This feature fundamentally and qualitatively distinguishes such oncogene-containing EVs from all of their counterparts that may be produced by transformed or non-transformed cellular populations, regardless of the state, function and origin of such cells. Indeed, this is the basis of the contention that EVs could …