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Fig. 3 | Molecular Cancer

Fig. 3

From: Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy

Fig. 3

Role of cytokines/chemokines on tumor progression and dissemination. High expression of CXCL12/CXCR4 axis in primary tumor cells or/and ECSCs enhances the activation of p-ERK-1/2 and increases these cells’ ability to invade and metastasize to lymph node and bone marrow. Abundant expression of CCL21 in the endothelium of lymphatic vessels and lymph nodes attracts CCR-7-positive tumor cells. CCL21/CCR7 axis upregulates MUC-1 expression through p-ERK signaling and enhances the migration, invasion, and lymph node metastasis through the lymphatic system. High production of potent angiogenic (VEGF-A) and lymphangiogenic (VEGF-C) factors by primary tumor cells leads to a malignant process. Elevated levels of CXCL-8 secreted by primary tumor cells or TAMs induces the phosphorylation of AKT and ERK1/2 signaling pathway through the CXCR2 receptor expressed in primary tumor cells. These processes lead to further malignant progression to lymph nodes and distant organ metastasis through the lymphatic system and blood vessel. Also, circulating CXCL-8 contributes to the metastasis process

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