HAPLN1 and melanoma: This reduction impairs the infiltration of both CD4+ and CD8+ T cells, thereby fostering an immunosuppressive environment conducive to melanoma progression.[76] Moreover, diminished HAPLN1 increases the permeability of lymphatic endothelial cells (LECs), promoting distant metastasis over lymph node involvement.[77] Besides, aged fibroblasts produce more secreted frizzled‐related protein 2 (sFRP2), a Wnt signaling antagonist that enhances both angiogenesis and metastasis of melanoma.