S100A4 and neoplasm: Precancerous lesions of LUAD are angiogenic, and pro-angiogenic factors secreted by cells, including S100a4+ alv-macro, induce endothelial cell sprouting and chemotaxis, leaving the angiogenic switch activated, prompting the formation of new blood vessels on the basis of the original ones to supply oxygen and nutrients to sustain tumor initiation (Chen et al., 2025; Kayser et al., 2003; van Hinsbergh and Koolwijk, 2008).