Potent phagocytic activity discriminates metastatic and primary human malignant melanomas: a key role of ezrin.
Features of phagocytosis have been observed in human tumors, but the phagocytic apparatus of tumor cells and the mechanism(s) underlying this phenomenon have yet to be defined. To address the phenomenon of phagocytosis, its underlying mechanism(s), and its possible role in tumor biology, we used human melanoma cells as a prototypic model. Our results showed that a process of phagocytosis of apoptotic cells occurs in vivo in human melanoma. This finding was consistent with evidence that human melanoma cells in vitro express all of the known lysosomal and phagocytic markers on their cytoplasmic vesicles and that a process of phagocytosis occurs in these vesicles. However, exclusively human melanoma cells deriving from metastatic lesions possess an efficient phagocytic machinery responsible for a macrophage-like activity against latex beads, yeast, and apoptotic cells of different origins, which was comparable to that of human primary macrophages. Moreover, the actin-binding protein ezrin was expressed on phagocytic vacuoles of melanoma cells and of cells deriving from a human adenocarcinoma; both treatment with cytochalasin B and specific inhibition of ezrin synthesis strongly affected the phagocytic activity of melanoma cells. This suggests that the association with the actin cytoskeleton is a crucial requirement for the development of this phenomenon. Hence our data provide evidence for a potent phagocytic activity exerted by metastatic melanoma cells possibly involved in determining the level of aggressiveness of human melanoma. This suggests that the assessment of phagocytic activity may be exploited as a new tool to evaluate the malignancy of human melanoma. Moreover, our data suggest that gene therapy or drug treatments aimed at inhibiting actin assembly to the phagosomal membranes may be proposed as a new strategy for the control of tumor aggressiveness.
Lugini
Luana
L
Laboratory of Immunology, Istituto Superiore di Sanità, Rome, Italy.
Lozupone
Francesco
F
Matarrese
Paola
P
Funaro
Cristina
C
Luciani
Francesca
F
Malorni
Walter
W
Rivoltini
Licia
L
Castelli
Chiara
C
Tinari
Antonella
A
Piris
Adriano
A
Parmiani
Giorgio
G
Fais
Stefano
S
D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers / Q000032:analysis; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D008545:Melanoma / Q000378:metabolism* / Q000556:secondary; D025581:Neurofibromin 2 / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology
D015415:Biomarkers; D025581:Neurofibromin 2