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S100 Soil Sensor Receptors and Molecular Targeting Therapy Against Them in Cancer Metastasis

Journal

TRANSLATIONAL ONCOLOGY
Volume 13, Issue 4, Pages -

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.tranon.2020.100753

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Funding

  1. JSPS KAKENHI [17H03577]
  2. Smoking Research Foundation
  3. Terumo Life Science Foundation
  4. Takeda Science Foundation
  5. Grants-in-Aid for Scientific Research [17H03577] Funding Source: KAKEN

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The molecular mechanisms underlying the 'seed and soil' theory are unknown. S100A8/A9 (a heterodimer complex of S100A8 and S100A9 proteins that exhibits a 'soil signal') is a ligand for Toll-like receptor 4, causing distant melanoma cells to approach the lung as a 'seeding' site. Unknown soil sensors for S100A8/A9 may exist, e.g., extracellular matrix metalloproteinase inducer, neuroplastin, activated leukocyte cell adhesion molecule, and melanoma cell adhesion molecule. We call these receptor proteins 'novel S100 soil sensor receptors (novel SSSRs).' Here we review and summarize a crucial role of the S100A8/A9-novel SSSRs' axis in cancer metastasis. The binding of S100A8/A9 to individual SSSRs is important in cancer metastasis via upregulations of the epithelial-mesenchymal transition, cellular motility, and cancer cell invasiveness, plus the formation of an inflammatory immune suppressive environment in metastatic organ(s). These metastatic cellular events are caused by the SSSR-featured signal transductions we identified that provide cancer cells a driving force for metastasis. To deprive cancer cells of these metastatic forces, we developed novel biologics that prevent the interaction of S100A8/A9 with SSSRs, followed by the efficient suppression of S100A8/A9mediated lung-tropic metastasis in vivo.

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