Stromal changes in the aged lung induce an emergence from melanoma dormancy

Area of Science:

• Oncology
• Cancer Metastasis
• Aging Biology

Background:

• Tumor dormancy is crucial for metastasis and residual disease in melanoma.
• Melanoma cells switch between proliferative and invasive states (phenotype switching).
• Age-related changes in microenvironments impact melanoma dissemination and growth.

Purpose of the Study:

• To characterize melanoma dormancy within the aged lung microenvironment.
• To identify molecular mechanisms driving melanoma dormancy and reactivation.
• To understand the role of WNT5A and fibroblast-secreted factors in melanoma metastasis.

Main Methods:

• Analysis of aged lung and skin microenvironments.
• Identification of signaling pathways involved in melanoma dormancy.
• Investigation of fibroblast-secreted factors and tyrosine kinase receptors.

Main Results:

• The aged lung microenvironment supports dormant melanoma cell outgrowth, unlike aged skin.
• WNT5A activates melanoma cell dormancy, facilitating dissemination and seeding.
• Age-induced lung fibroblasts secrete sFRP1, inhibiting WNT5A and promoting metastatic outgrowth.
• Tyrosine kinase receptors AXL and MER mediate melanoma cell dormancy-to-reactivation.

Conclusions:

• Age-induced changes in distal metastatic sites, particularly the lung, promote melanoma dormancy and reactivation.
• WNT5A signaling is a key regulator of melanoma dormancy and metastatic outgrowth in the aged lung.
• Targeting WNT5A and associated pathways may offer strategies to prevent or treat melanoma metastasis.