(A) Secretion of specific laminin (LAM) isoforms facilitates carcinoma initiation and re-initiation at metastatic sites by activating β1 integrin signaling. Tenascin-C (TNC) and periostin (POSTN) are also key stromal elements promoting metastatic reactivation.
(B) Stromal elements and cancer cells cooperate to deposit the extracellular matrix of metastatic niches through several mechanisms including neutrophil extracellular trap (NET) remodeling. LAM, fibronectin (FN), POSTN, and TNC––acting through integrins, Syndecan-4 (SDC4), and the Wnt receptor Frizzled (FZD)––activate signaling pathways involved in metastatic outgrowth.