(A) At the site of established growing tumors, Ang2 acts as an angiogenesis initiator, while exogenous Ang1 diminishes the anti‐tumor efficacy of anti‐angiogenic anti‐VEGF and anti‐Ang2 therapies (Falcón et al,
2009; Huang et al,
2009; Coxon et al,
2010; Daly et al,
2013). (B) At the destination sites of metastasis, Ang2 de‐stabilizes the "normal" host blood vessels to facilitate various steps in the metastatic cascade (Talmadge & Fidler, 2010). (1) Tumor cell adhesion to capillary wall (Kim et al,
2001); (2) tumor cell extravasation (Gavard et al,
2008); and (3) tumor cell co‐option of existing host vessels (Holash et al,
1999). We thus hypothesize that Ang1, a vascular stabilizing factor, may inhibit these early metastatic events, i.e., in the lung: (1') inhibition of cancer cell adhesion and arrest (Michael et al,
2017); and (2') inhibition of extravasation due to stabilized vessels (Wu et al,
2015).