The molecular basis of melanoma metastasis to sentinel nodes
Cutaneous melanoma first metastasizes into sentinel lymph nodes that control the lymphatic drain from the area of the primary tumor. Sentinel lymph node biopsy has therefore become an important and routinely performed diagnostic procedure in patients with primary melanomas thicker than 1mm (tumor stage ≥T2a). The importance of sentinel node analysis is reflected by a significant better prognosis of melanoma patients with tumor free sentinel nodes compared to patients with metastatic sentinel nodes. Successful colonization of tumor cells into sentinel lymph nodes is thought to require priming of this environment, but these priming factors are yet undefined.
We aim to identify and analyze a gene expression signature reflecting priming events. We will use a mouse xenotransplantation model, in which human M24met melanoma cells grafted into the skin of SCID mice metastasize to sentinel lymph nodes. This model allows separate analysis of human and mouse genes. Results are correlated with specimens of sentinel nodes from human patients. In a next step, potential targets will be tested for their biological relevance in lymph node priming processes in vitro and in vivo.
This approach offers two long term perspectives:
- Identification of new prognostic factors
- Establishment of a novel therapeutic approach preventing melanoma cells from colonizing sentinel lymph node
Lymph nodes are screened for the presence of human melanoma cells and gene expression patterns of melanoma cells and stromal cells are determined.
Publications
- Dimethylfumarate impairs melanoma growth and metastasis.
Loewe R, Valero T, Kremling S, Pratscher B, Kunstfeld R, Pehamberger H, Petzelbauer P. Cancer Res. 2006 Dec 15;66(24):11888-96.
Team
- Robert Loewe, M.D.
- Andreas Bracher, DI (FH)
- Ana Soler Cardena, M.D.
