Figure 4.

 Expansion of the S100A8‐SAA3 paracrine field in the lungs. The S100A8–serum amyloid A3 (SAA3) paracrine system that is stimulated in an endocrine fashion by growth factors produced by primary tumors recruits bone marrow‐derived myeloid cells (BMDC). The paracrine system is supposed to expand until those Toll‐like receptor 4 (TLR4) agonists cause expression of TNFα in the lungs, making that derived from primary tumors dispensable for the preparation of pre‐metastatic (pre‐meta.) soil. Tumor cells from the primary site may arrive after maturation of pre‐metastatic soil. Alternatively, tumor cells and BMDC work in concert to prepare the soil. In this case, tumor cell arrival and soil preparation proceed simultaneously and it is beyond discussion which comes first, BMDC or tumor cells.^{( 72 )}