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Overexpression of LLT1 (OCIL, CLEC2D) on prostate cancer cells inhibits NK
cell-mediated killing through LLT1-NKRP1A (CD161) interaction
#MMPMID27626681
Mathew SO
; Chaudhary P
; Powers SB
; Vishwanatha JK
; Mathew PA
Oncotarget
2016[Oct]; 7
(42
): 68650-68661
PMID27626681
show ga
Prostate cancer is the most common type of cancer diagnosed and the second
leading cause of cancer-related death in American men. Natural Killer (NK) cells
are the first line of defense against cancer and infections. NK cell function is
regulated by a delicate balance between signals received through activating and
inhibitory receptors. Previously, we identified Lectin-like transcript-1
(LLT1/OCIL/CLEC2D) as a counter-receptor for the NK cell inhibitory receptor
NKRP1A (CD161). Interaction of LLT1 expressed on target cells with NKRP1A
inhibits NK cell activation. In this study, we have found that LLT1 was
overexpressed on prostate cancer cell lines (DU145, LNCaP, 22Rv1 and PC3) and in
primary prostate cancer tissues both at the mRNA and protein level. We further
showed that LLT1 is retained intracellularly in normal prostate cells with
minimal cell surface expression. Blocking LLT1 interaction with NKRP1A by
anti-LLT1 mAb on prostate cancer cells increased the NK-mediated cytotoxicity of
prostate cancer cells. The results indicate that prostate cancer cells may evade
immune attack by NK cells by expressing LLT1 to inhibit NK cell-mediated
cytolytic activity through LLT1-NKRP1A interaction. Blocking LLT1-NKRP1A
interaction will make prostate cancer cells susceptible to killing by NK cells
and therefore may be a new therapeutic option for treatment of prostate cancer.
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