Fig. S1 from Metastatic Conditioning of Myeloid Cells at a Subcutaneous Synthetic Niche Reflects Disease Progression and Predicts Therapeutic Outcomes

Development of the pre-metastatic niche (preMN), metastatic niche (MN), and synthetic diagnostic site. Circulating tumor cells exhibit a tropism for specific distal microenvironments, thus indicating that metastasis is pre-determined. Development of these predetermined sites is driven by (1) systemic conditioning from the primary tumor through secretion of factors and exosomes, which is amplified by simultaneous conditioning of the bone-marrow and alterations in bone-marrow derived cells. (2) This process conditions distal tissues and contributes to the (3) aggregation of pre-metastatic immune cells and extracellular matrix proteins. (4) These primed distal microenvironments are denoted as the preMN and facilitate homing then colonization of (5) circulating tumor cells which (6) extravasate and (7) migrate into distal organs where they may become a (8) disseminated tumor cells if the conditions are hospitable. This disseminated tumor cell may then undergo a phenotypic shift to initiate a (9) metastatic secondary growth, thus leading to development of a metastatic niche. Given that the preMN contains a unique mixture of soluble factors, extracellular matrix, stromal and immune cells (e.g., cancer-associated fibroblasts and myeloid-derived suppressor cells, MDSCs), it is reasonable that preMN function could be synthesized through the recapitulation these unique factors at a synthetic site in vivo. This rationale underpins the development of material based synthetic diagnostic site that (2.1) is conditioned, (3.1) populated by disease associated immune cells, (4.1) develops characteristics of a preMN, and (7.1) captures metastatic tumor cells.