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S100A8/A9 provides a premetastatic environment. S100A8/A9 expresses on tumor cells and also inflammatory cells. S100A8/A9–RAGE interaction results in activation of Smad, NF-κB, ERK1/ERK2, and SAPK/JNK pathways and increasing the leukocyte recruitment angiogenesis, tumor migration, and wound healing and consequently providing premetastatic niches. MDSCs will promote immunosuppressive microenvironment by activation of NF-κB pathway and also cause chemotaxis by P38 activation.
