BoneKEy Reports | BoneKEy Watch
Targeting L1CAM and DDR1 may reduce bone metastasis in NSCLC
DOI:10.1038/bonekey.2012.75
Expression of the L1 cell adhesion molecule (L1CAM) is associated with reduced survival in non-small-cell lung cancer (NSCLC). After confirming this association using published microarrays from 674 NSCLC patients, Hai et al. showed that cells with reduced L1CAM expression were significantly less able to migrate into a wound in the cultured cell monolayer, or to invade a basement membrane.
L1CAM may exert its effects via the extracellular-signal regulated kinase (Erk) pathway. In vivo studies revealed that tumor cells with reduced L1CAM expression were significantly less able to produce tumors in severe combined immunodeficiency (SCID) mice and did not metastasize to bone and other distant sites as easily in an orthotopic nude rat model.
Valencia et al. investigated discoidin domain receptor-1 (DDR1), a collagen binding receptor also associated with poor prognosis in NSCLC. They showed that cells lacking DDR1 were less likely to produce metastatic tumors or to induce osteolytic lesions in an in vivo model of bone metastasis. Furthermore, injecting knockdown DDR1 cells into the metastatic mouse model reduced tumor burden significantly.
Editor's comment: Lung cancer is prone to metastasize to bone. These studies show that L1CAM and DDR1 expression in primary non-small-cell lung cancer is associated with poor prognosis, and that the silencing of L1CAM or DDR1 reduces the metastatic spread of human lung cancer cells in bone in animal models. L1CAM and DDR1 may therefore represent promising targets for treatment of lung cancer bone metastasis.
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