Waking up melanoma
Source: Science Signaling, June 2022
Abstract
Dormant melanoma cells in the lung can be reactivated by age-related environmental cues in the stroma.
Melanoma cells may undergo a phenotypic switch between a proliferative state and a slow and invasive one, resulting in growth and dissemination. Skin fibroblasts may facilitate phenotypic switching in primary tumors; however, the role of lung fibroblasts in age-related metastatic melanoma is unclear. Noting that primary melanoma tumor progression and metastatic outgrowth increase with age, Fane et al. investigated the role of metastatic lung fibroblasts in this phenomenon. Melanoma cells intradermally grafted into older mice showed greater metastatic efficiency than those grafted into younger mice, and aged lung fibroblasts better promoted melanoma growth compared to young fibroblasts, whereas aged skin fibroblasts suppressed growth. Proteomic analysis showed that a noncanonical WNT antagonist, sFRP1, was secreted by aged human lung fibroblasts. WNT5A was implicated in age-related melanoma dormancy in primary tumors. Mice were intradermally grafted with melanoma cells, and, at the point of single-cell seeding in lungs, were treated with an sFRP1-neutralizing antibody, which resulted in reduced metastatic colony formation and proliferation.