Finding additional functional targets for combination therapy could improve the outcome for melanoma patients.,In a spontaneous metastasis xenograft model of human melanoma a shRNA mediated knockdown of L1CAM more than sevenfold reduced the number of lung metastases after the induction of subcutaneous tumors for two human melanoma cell lines (MeWo, MV3).,Whole genome expression arrays of the initially L1CAM high MeWo subcutaneous tumors revealed unchanged or downregulated genes involved in epithelial to mesenchymal transition (EMT) except an upregulation of Jagged 1, indicating a compensatory change in Notch signaling especially as Jagged 1 expression showed an increase in MeWo L1CAM metastases and Jagged 1 was expressed in metastases of the initially L1CAM low MV3 cells as well.,Expression of 17 genes showed concordant regulation for L1CAM knockdown tumors of both cell lines.,The changes in gene expression indicated changes in the EMT network of the melanoma cells and an increase in p53/p21 and p38 activity contributing to the reduced metastatic potential of the L1CAM knockdowns.,Taken together, these data make L1CAM a highly interesting therapeutic target to prevent further metastatic spread in melanoma patients.
Melanoma is a form of cancer that initiates in melanocytes.,Melanoma has multiple phenotypically distinct subpopulation of cells, some of them have embryonic like plasticity which are involved in self-renewal, tumor initiation, metastasis and progression and provide reservoir of therapeutically resistant cells.,Cancer stem cells (CSCs) can be identified and characterized based on various unique cell surface and intracellular markers.,CSCs exhibit different molecular pattern with respect to non-CSCs.,They maintain their stemness and chemoresistant features through specific signaling cascades.,CSCs are weak in immunogenicity and act as immunosupressor in the host system.,Melanoma treatment becomes difficult and survival is greatly reduced when the patient develop metastasis.,Standard conventional oncology treatments such as chemotherapy, radiotherapy and surgical resection are only responsible for shrinking the bulk of the tumor mass and tumor tends to relapse.,Thus, targeting CSCs and their microenvironment niche addresses the alternative of traditional cancer therapy.,Combined use of CSCs targeted and traditional therapies may kill the bulk tumor and CSCs and offer a promising therapeutic strategy for the management of melanoma.