Why is melanoma so metastatic?

Abstract

Summary Malignant melanoma is one of the most aggressive cancers and can disseminate from a relatively small primary tumor and metastasize to multiple sites, including the lung, liver, brain, bone, and lymph nodes. Elucidating the molecular and genetic changes that take place during the metastatic process has led to a better understanding of why melanoma is so metastatic. Herein, we describe the unique features that distinguish melanoma from other solid tumors and contribute to the malignant phenotype of melanoma cells. For example, although melanoma cells are highly antigenic, they are extremely efficient at evading host immune response. Melanoma cells share numerous cell surface molecules with vascular cells, are highly angiogenic, are mesenchymal in nature, and possess a higher degree of ‘stemness’ than do other solid tumors. Finally, analysis of melanoma mutations has revealed that the gene expression profile of malignant melanoma is different from that of other cancers. Elucidating these molecular and genetic processes in highly metastatic melanoma can lead to the development of improved treatment and individualized therapy options.

Increased Angiogenesis and Lymphangiogenesis in Metastatic Sentinel Lymph Nodes Is Associated With Nonsentinel Lymph Node Involvement and Distant Metastasis in Patients With Melanoma

“…It indeed has been shown that melanoma cells that have the ability to detach from the primary tumor and intravasate into blood or lymphatic vessels, have many antigens in common with vascular endothelial cells, such as melanoma cell adhesion molecules, N-cadherin, vascular cell adhesion molecule, intracellular adhesion molecule, platelet endothelial cell adhesion molecule and vascular endothelial-cadherin, allowing melanoma cells to survive the physical forces within the circulation, adhere to the vessel wall within distant organs, and extravasate into the parenchyma. 28,29 The second possible reason is that because of the inclusion criteria (available histological material), most of the included patients presented with large and extensive SLN metastasis with expected high oxygen and nutrient needs, justifying the highly angiogenic phenotype of metastatic cells.…”

Enhancer methylation dynamics contribute to cancer plasticity and patient mortality

“…We were curious what would occur to DNA methylation patterns of cells that disseminate from the primary location and colonize in metastatic sites. To evaluate this, we focused on melanoma, a highly metastatic cancer (Braeuer et al 2014). We compared methylation data from metastatic melanoma patients (seven distinct locations) to data from patients with primary in situ melanoma (Supplemental Table S1).…”

The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors

“…Its aggressiveness is based on the highly metastatic potential of melanoma cells, which can still not be efficiently targeted despite recent progress in melanoma therapies 2 . In fact, currently available drugs frequently induce resistance 3 and have even been shown to promote invasiveness and metastasis of resistant cells 4 .…”