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2018 ; 12
(1
): 55-68
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CD99 at the crossroads of physiology and pathology
#MMPMID29305692
Pasello M
; Manara MC
; Scotlandi K
J Cell Commun Signal
2018[Mar]; 12
(1
): 55-68
PMID29305692
show ga
CD99 is a cell surface protein with unique features and only partly defined
mechanisms of action. This molecule is involved in crucial biological processes,
including cell adhesion, migration, death, differentiation and diapedesis, and it
influences processes associated with inflammation, immune responses and cancer.
CD99 is frequently overexpressed in many types of tumors, particularly pediatric
tumors including Ewing sarcoma and specific subtypes of leukemia. Engagement of
CD99 induces the death of malignant cells through non-conventional mechanisms. In
Ewing sarcoma, triggering of CD99 by specific monoclonal antibodies activates
hyperstimulation of micropinocytosis and leads to cancer cells killing through a
caspase-independent, non-apoptotic pathway resembling methuosis. This process is
characterized by extreme accumulation of vacuoles in the cytoplasmic space, which
compromises cell viability, requires the activation of RAS-Rac1 downstream
signaling and appears to be rather specific for tumor cells. In addition,
anti-CD99 monoclonal antibodies exhibit antitumor activities in xenografts in the
absence of immune effector cells or complement proteins. Overall, these data
establish CD99 as a new opportunity to treat patients with high expression of
CD99, particularly those that are resistant to canonical apoptosis-inducing
agents.
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