Expression of the
L1 cell adhesion molecule (
L1CAM) is frequently increased in
cancer patients compared to healthy individuals and also linked with bad prognosis of solid tumours. Previously, we could show that full-length
L1CAM promotes
metastasis formation via up-regulation of gelatinolytic activity in
fibrosarcoma. In this study, we aimed to extend this finding to haematogenous
malignancies and
carcinomas, and to specifically elucidate the impact of
L1CAM on major steps of the metastatic cascade. In a well-established
T-cell lymphoma spontaneous
metastasis model, silencing of
L1CAM significantly improved survival of the mice, while intradermal tumour growth remained unaltered. This correlated with significantly decreased spontaneous
metastasis formation.
L1CAM suppression abrogated the metastatic potential of
T-cell lymphoma as well as
carcinoma cells as demonstrated by reduced migration and invasion in vitro and reduced formation of experimental
metastasis in vivo. At the molecular level, silencing of
L1CAM led to reduced expression of
gelatinases MMP-2 and -9 in vitro and decreased gelatinolytic activity in primary tumours and
metastases in vivo. In accordance, knock down of
L1CAM had similar suppressive effects on migration, invasion and in vivo-gelatinolytic activity as treatment with the specific
gelatinase inhibitor SB-3CT. This newly discovered impact of
L1CAM on distinct steps of the metastatic cascade and
MMP activity highlights the potential of possible L1CAM-directed
therapies to inhibit metastatic spread.