Tumor necrosis factor superfamily member 14 (TNFSF14), LIGHT
is one of the cytokines produced by tumor and immune cells, which
promotes homeostasis of lymphoid organs, liver and bone. Nonsmall cell lung cancer (NSCLC) commonly metastasizes bone, altering
bone homeostasis and causing osteolysis. Here we investigated the
role of LIGHT in NSCLC-induced osteolytic bone disease.
The LIGHT expression in monocytes was higher in patients with
metastatic bone lesions than in non-bone metastatic ones (66.5 ±
24.5 vs 43.3 ± 25.2 mean ± SD, p = 0.001), in healthy donors
(66.5 ± 24.5 vs 8.5 ± 4.6 p = 0.0002), and in non-bone metastatic
patients than in healthy donors (43.3 ± 25.2 vs 8.5 ± 4.6, p =
0.0001). Serum LIGHT levels were also significantly higher in
bone metastatic patients than in non-bone metastatic ones
(186.8 ± 191.2 pg/ml vs 115.8 ± 73 pg/ml, p = 0.04) and in healthy
donors (186.8 ± 191.2 pg/ml vs 85.7 ± 38.4 pg/ml, p = 0.04).
A neutralizing mAb anti-LIGHT added to osteoclast (OC) cultures of
both bone and non-bone metastases inhibited osteoclastogenesis, but
the decrease was statistically significant only for bone metastatic
patients (272 ± 98 vs 132 ± 74, p = 0.01). To investigate the role of
LIGHT in NSCLC- induced bone lesion in vivo, we performed an
intratibial injection of a mouse lung cancer cell line LLC-1, in wild-type
(WT) and LIGHT KO mice. The WT-injected mice displayed a significant
reduction of about 20% for BV/TV, Tb.N, Tb.Th, and Tb.Sp compared to
the WT-vehicle mice (pb 0.01). These parameters did not show
significant variation for KO-injected mice vs vehicle or for WT-injected
mice vs KO-injected mice. These data indicate LIGHT as a regulator of
bone homeostasis during NSCLC metastatic invasion, thus it may be a
novel therapeutic target in osteolytic bone metastases
