Melanoma cells can attack using microvesicles loaded with FasL (red).

Fais/RUP

Melanoma cells send out microvesicles loaded with Fas ligand (FasL) to kill their would-be assassins, according to Stefano Fais (Istituto Superiore di Sanità, Rome, Italy), Licia Rivoltini (Istituto Nazionale dei Tumori, Milan, Italy), and colleagues.

The FasL hijacks a normal transport pathway for melanin, the pigment that melanosomes load into microvesicles and send to neighboring keratinocytes. In melanoma cells, these microvesicles, or exosomes, are also loaded with FasL, which can trigger apoptosis in Fas-expressing immune cells that might otherwise counteract tumor growth.

This mechanism of counterattack may operate in other tumors, as microvesicles are released from a number of cell types. In the case of melanoma cells, the new work clears up a controversy. Microvesicles explain how melanoma cells can have an apoptotic effect (the initial observation) without expressing FasL on their cell surface (the subsequent, seemingly contradictory observation).

Although purified microvesicles can kill cultured Fas-expressing cells, the same cells are not killed by coculture with melanoma cells. This suggests that, in vivo, some other microenvironmental factors may either provoke a higher level of microvesicle production or optimize the effects of the killer exosomes. Fais also hopes to determine how the Fas-expressing melanoma cells manage to avoid killing themselves with their own microvesicles. ▪

Reference:

Andreola, G., et al.
2002
.
J. Exp. Med.
195
:
1303
–1316.