Caveolin-1 is a risk factor for postsurgery metastasis in preclinical melanoma models.
Melanomas are highly lethal skin tumours that are frequently treated by surgical resection. However, the efficacy of such procedures is often limited by tumour recurrence and metastasis. Caveolin-1 (CAV1) has been attributed roles as a tumour suppressor, although in late-stage tumours, its presence is associated with enhanced metastasis. The expression of this protein in human melanoma development and particularly how the presence of CAV1 affects metastasis after surgery has not been defined. CAV1 expression in human melanocytes and melanomas increases with disease progression and is highest in metastatic melanomas. The effect of increased CAV1 expression can then be evaluated using B16F10 murine melanoma cells injected into syngenic immunocompetent C57BL/6 mice or human A375 melanoma cells injected into immunodeficient B6Rag1-/- mice. Augmented CAV1 expression suppresses tumour formation upon a subcutaneous injection, but enhances lung metastasis of cells injected into the tail vein in both models. A procedure was initially developed using B16F10 melanoma cells in C57BL/6 mice to mimic better the situation in patients undergoing surgery. Subcutaneous tumours of a defined size were removed surgically and local tumour recurrence and lung metastasis were evaluated after another 14 days. In this postsurgery setting, CAV1 presence in B16F10 melanomas favoured metastasis to the lung, although tumour suppression at the initial site was still evident. Similar results were obtained when evaluating A375 cells in B6Rag1-/- mice. These results implicate CAV1 expression in melanomas as a marker of poor prognosis for patients undergoing surgery as CAV1 expression promotes experimental lung metastasis in two different preclinical models.
aCellular Communication Laboratory, Center for Molecular Studies of the Cell (CEMC), Advanced Center for Chronic Diseases (ACCDiS), School of Medicine, Universidad de Chile bDepartment of Surgery, Hospital Clinico Universidad de Chile cAndes Biotechnologies, Fundación Ciencias y Vida dSchool of Biological Sciences, Universidad Andres Bello, Santiago, Chile eDivision of Biomedical Sciences, St. George's, University of London, London, UK fFreie Universität Berlin - Institut für Pharmakologie, Berlin, Germany.
Lorena
L
Lobos-Gonzalez
Lorena
L
Aguilar-Guzmán
Jaime G
JG
Fernandez
Nicolas
N
Muñoz
Mehnaz
M
Hossain
Simone
S
Bieneck
Veronica
V
Silva
Veronica
V
Burzio
Elena V
EV
Sviderskaya
Dorothy C
DC
Bennett
Lisette
L
Leyton
Andrew F G
AF
Quest
D000818:Animals; D051242:Caveolin 1 / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D008545:Melanoma / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology / Q000601:surgery*
C495540:CAV1 protein, human; C495541:Cav1 protein, mouse; D051242:Caveolin 1