Figure 2. Putative role of malignant melanoma-initiating cells (MMICs) in metastatic progression.

In addition to primary tumor formation, increasing evidence suggests that MMICs may play a crucial role in the “invasion-metastasis cascade.” After dissociation from the primary tumor and subsequent intravasation into the blood stream or lymphatic system, MMICs are enriched among circulating tumor cells (CTCs) and may home to distant tissues to promote metastatic seeding and also propagate macrometastasis formation. This would be consistent with the finding of increased MMIC frequencies in metastatic compared to primary melanomas.