Scientists at Tel Aviv University and the Sheba Medical Center at Tel Hashomer have identified how melanoma — the deadliest form of skin cancer — engineers its own escape route through the body. The finding, published in the Journal of Investigative Dermatology, points toward a possible vaccine-based approach to stopping the cancer before it spreads.
At a glance
- Melanoma metastasis: Researchers showed for the first time that melanoma cells release tiny vesicles called melanosomes while still in the outer skin layer, before the cancer has reached the deeper dermis.
- Lymphangiogenesis: Those melanosomes travel into the dermis and signal lymph vessel cells to multiply and migrate — effectively building new roads the cancer later uses to spread.
- Melanoma vaccine: Because melanoma confined to the skin is not life-threatening, the team believes a vaccine that trains the immune system to neutralize melanosomes could block metastasis at its source.
What the researchers found
Melanoma starts in the epidermis, the skin’s outermost layer, when melanocyte cells begin dividing without control. The cancer only becomes life-threatening when it breaks through into the dermis and escapes via the lymphatic and blood systems. Earlier studies had noticed a sharp rise in lymph vessel density around melanoma tumors, but no one had explained why — until now.
The team, led by Prof. Carmit Levy of Tel Aviv University’s Faculty of Medicine and Prof. Shoshana Greenberger of Sheba Medical Center, found that melanoma cells secrete melanosomes — small, pigment-carrying extracellular vesicles — while still in the epidermis. Those vesicles then travel down into the dermis and enter lymph vessel cells, where they trigger the cells to replicate and migrate.
“Melanoma cells secrete the melanosomes before cancer cells reach the dermis layer of the skin,” Levy explained. “These vesicles modify the dermis environment to favor cancer cells, so melanoma cells are responsible for enriching the dermis with lymph vessels and preparing the substrate for their own metastasis.”
In plain terms: the tumor is building its own highway network before it even needs to use it.
Why this opens a new treatment direction
The key insight is one of timing. Because melanoma at the premetastatic stage — while it remains in the epidermis — is not dangerous, any therapy that can interrupt the process before the cancer spreads could change outcomes dramatically.
“Melanoma that remains on the skin is not dangerous,” Greenberger said. “So the most promising direction for fighting melanoma is immunotherapy — developing a vaccine that will arouse the immune system to combat the melanosomes and specifically to attack the lymphatic endothelial cells already invaded by the melanosomes. If we can stop the mechanisms that generate metastases in lymph nodes, we can also stop the disease from spreading.”
The study was funded by the Israel Cancer Research Fund and published under the title “Primary melanoma miRNAs trafficking induce lymphangiogenesis” in Nature’s Journal of Investigative Dermatology. The research examined human melanoma samples from a pathology institute to confirm that melanosomes do penetrate lymph vessels under real biological conditions — not just in lab models.
What comes next
Follow-on studies already underway suggest the melanosomes reach further than the lymphatic system. Early results show they also affect the immune system, widening the potential scope of both the threat and the therapeutic opportunity.
That wider reach may eventually help researchers design more targeted interventions — treatments that disrupt not just the lymph vessel expansion but also the immune suppression that allows the cancer to evade detection.
It is important to be clear about where this research stands. The study describes a biological mechanism and a plausible vaccine concept; no vaccine has been developed or tested in clinical trials yet. The path from a mechanistic discovery to a working immunotherapy is long, and this finding — significant as it is — represents an early step on that road. Still, identifying precisely how and when melanoma prepares its escape gives scientists a sharper target than they had before.
Melanoma is diagnosed in roughly 325,000 people worldwide each year, according to the World Health Organization, and its incidence has been rising in many countries. New therapeutic strategies — especially those that act early, before metastasis occurs — are urgently needed. Research into melanoma immunotherapy has accelerated globally over the past decade, with several checkpoint inhibitors already extending survival. A vaccine that targets the metastatic mechanism itself would be a meaningful addition to that toolkit.
The Tel Aviv University and Sheba Medical Center collaboration reflects a broader strength in Israeli oncology research, which has produced several advances in cancer biology in recent years — part of a global scientific effort to shift cancer treatment from reactive to preventive.
Read more
For more on this story, see: The Jerusalem Post
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