How melanoma silences the skin's natural antitumor defense
Cancers actively remodel their surrounding cells and tissues to create a microenvironment that favors their growth, survival and spread. Melanoma, a cancer of the pigment-producing melanocytes of the skin, is one of the most aggressive skin cancers and can rapidly metastasize if not detected and treated early.
Melanoma, a type of skin cancer, actively alters the microenvironment around it to promote its growth and spread. Keratinocytes, the most abundant cells in the skin, are located near melanoma cells and are essential for protecting against melanoma. However, research published in Cell Reports suggests that melanoma cells actively suppress the protective function of keratinocytes.
This suppression occurs through the release of exosomes containing the miRNA hsa-miR-221-5p, which reduces the production of LL-37, a protective antimicrobial peptide produced by keratinocytes. When LL-37 is suppressed, melanoma cells can grow and spread more easily. This mechanism weakens a local antitumor defense pathway called EGFR, which would otherwise restrain tumor progression.
Melanoma-derived exosomes carrying hsa-miR-221-5p suppress LL-37 production in adjacent keratinocytes, weakening EGFR-associated local antitumor defense. LL-37 has been found to counteract melanoma progression by suppressing cell proliferation and spread, as well as recruiting beneficial immune cells. This study suggests that strengthening epithelial defense mechanisms, such as LL-37 expression, may offer a complementary therapeutic strategy for melanoma.
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