Updated project metadata. Detachment of melanoma and survival under anchorage-independency were recognized as initial step of tumor metastasis. Our previous studies showed altered gene expression contributed to loss of cell invasiveness, enhanced chemosensitivity, and enhanced subcutaneous tumor formation. In this study, we demonstrated that melanoma cell detachment altered vascular phenotype of melanoma metastases through disruption of expression axis of aminopeptidase-N/syndecan-1/integrin beta4, which would contribute to melanoma heterogeneity.