As discussed in more detail below and summarized in Figure 5, our study is unique and significant in that we have shown that (i) the ANP-GC-A signaling prevents cancer metastasis in two different models (Figure 1 and Supplementary Figure 1), (ii) a role for ANP in globally inhibiting up-regulation of pre-metastatic niche factors is context-specific: no hazardous effects on lung gene expression in the absence of cancer (Figures 2–4), (iii) the host ANP-GC-A signaling in endothelial cells is genetically essential for antagonizing pre-metastatic niche formation in the lung (Figure 4). Here, NPPA is linked to cancer.