BACKGROUND: Endothelin-3 (ET-3) is an essential paracrine factor for the proliferation, migration, and survival of embryonic melanocytes during fetal development. Its expression is tightly regulated, being completely turned off in adult skin. OBJECTIVE: In this study, results are presented that demonstrate abnormal expression of ET-3 by metastatic melanoma cells in both tissue biopsies and cell culture. Further, in vitro experiments showed that metastatic melanoma cells have the capacity to respond to ET-3 stimulation by increasing survival. CONCLUSION: Therefore, an abnormal autocrine stimulation pathway involving ET-3 is present in metastatic melanoma cells. Blocking this signal transduction pathway may prove useful for the treatment of metastatic melanoma.
BACKGROUND:Endothelin-3 (ET-3) is an essential paracrine factor for the proliferation, migration, and survival of embryonic melanocytes during fetal development. Its expression is tightly regulated, being completely turned off in adult skin. OBJECTIVE: In this study, results are presented that demonstrate abnormal expression of ET-3 by metastatic melanoma cells in both tissue biopsies and cell culture. Further, in vitro experiments showed that metastatic melanoma cells have the capacity to respond to ET-3 stimulation by increasing survival. CONCLUSION: Therefore, an abnormal autocrine stimulation pathway involving ET-3 is present in metastatic melanoma cells. Blocking this signal transduction pathway may prove useful for the treatment of metastatic melanoma.
Authors: Aleksandar Sekulic; Paul Haluska; Arlo J Miller; Josep Genebriera De Lamo; Samuel Ejadi; Jose S Pulido; Diva R Salomao; Erik C Thorland; Richard G Vile; David L Swanson; Barbara A Pockaj; Susan D Laman; Mark R Pittelkow; Svetomir N Markovic Journal: Mayo Clin Proc Date: 2008-07 Impact factor: 7.616