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Page 4 of 11 Mizejewski. J Cancer Metastasis Treat 2019;5:35 I http://dx.doi.org/10.20517/2394-4722.2018.70

Figure 1. Peptide disruption of tumor to stroma communication. The peptide disruption of the tumor-to-stromal cell communication
network is displayed together with the connective tissue layers, cell components, and signaling pathways. Note that the top half of the
diagram displays the communication network connection indicated by the dashed lines (---) between tumor/stromal cells; while the
bottom second half demonstrates the blocked linkage(←--X-→) due to peptide disruption of tumor-to-stoma communication (see text
for references and Ref.[45])

involved in cell mobility, migration, adhesion, platelet aggregation, and cell-to-cell contact; such processes
[19]
occur during reproduction, neurogenesis, muscle development, and tumorigenesis . The collagenases
and gelatinases are family members involved in tissue remodeling, bone mineralization, reproduction,
[20]
autoimmune diseases, inflammation, and cancer development . The integrins are composed of alpha/beta
[21]
chain proteins that participate in cell adhesion/contact and ECM-to-cell membrane inside-out signaling .
2+
[22]
Finally, annexins are Ca and phospholipid binding proteins that serve in blood coagulation processes .
The growth factor receptor family proteins
The growth factor receptors associated with the tumor microenvironment and metastatic sites are largely
G-coupled seven-transmembrane receptors containing kinase domains required for intracellular signaling
[23]
and cross-talk between adjacent pathways [Table 1]. These receptors bind growth factors such as fibroblast