Fig. 2.

Schematics of mutual communication between cancer cells, tumor associated host cells and ecosystems. a Schematic of communication between cancer cells and tumor-associated host cells with invasion-related radiation-sensitive molecules. Arrows indicate the communication between cancer cells and tumor-associated host cells, namely fibroblasts, macrophages, lymphocytes, adipocytes, osteoclasts and endothelial cells, and between tumor-associated host cells, for example fibroblasts to endothelial cells. White text boxes overlapping the arrows contain the molecules implicated in this communication and shown to be sensitive to alterations by radiation. This intercellular communication establishes the individual local ecosystems that participate at metastasis as shown in panel b Adapted from Mareel et al., (2009b), with data from: Vakaet (2004); Abdollahi (2005); Chargari et al., (2013); De Bacco et al., (2011b); Gu et al., (2015b); Hamalukic et al., (2011b); Hirschhaeuser et al., (2011); Kuonen et al., (2012a); Li et al., (2016b); Madani et al., (2008); Nubel (2004); Vilalta (2016); Lee et al., (2017c). b Schematic of the communication between ecosystems of primary tumor, distant metastasis, lymph node and bone marrow, associated with metastasis and sensitive to ionizing radiation. Arrows indicate the communication between ecosystems, namely the primary tumor, lymph node, distant metastasis and bone marrow. Participating at this communication are host cells (smaller green ovals), cancer cells (smaller pink ovals) and molecules (white text boxes), all implicated in radiation-enhanced metastasis. Adapted from: Madani et al., (2008); Ceelen et al., (2014) and Willaert et al., (2014) with data from: Kioi et al., (2010b); Kuonen et al., (2012c); Russell & Brown (2013b); Vilalta (2016). Abbreviations: CC, cancer cells; CCL, C-C motif chemokine ligand; CSF1, macrophage colony-stimulating factor 1; CTC, circulating tumor cells; CXCL, C-X-C motif chemokine ligand; DC, dendritic cells; DTC,disseminated tumor cells; EPC, endothelial precursor cells; FGF2, basic fibroblast growth factor; GMCSF, granulocyte-macrophage colony-stimulating factor; HGF, hepatocyte growth factor; HSC, hematopoietic stem cells; IGF1, insulin-like growth factor 1; IL, interleukin; LC, lymphocytes; MCC, metastatic cancer cells; MMP, matrix metalloproteinase; MSC, mesenchymal stem cells; OPN, osteoprotogerin; PDGF, platelet-derived growth factor; PlGF, placental growth factor; RANKL, receptor activator of nuclear kappa-B ligand; SC, stem cells; S-Lewis A, sialyl-Lewis A antigen; SCF, stem cell factor; SDF1 (also called CXCL12), stromal- cell derived factor 1; sVCAM1, soluble vascular cell adhesion molecule 1; TGFβ, transforming growth factor beta; TNFα, tumor necrosis factor-alpha; VEGF, vascular endothelial growth factor