Mini-Review: Can the Metastatic Cascade Be Inhibited by Targeting CD147/EMMPRIN to Prevent Tumor Recurrence?

Abstract

Solid tumors metastasize very early in their development, and once the metastatic cell is lodged in a remote organ, it can proliferate to generate a metastatic lesion or remain dormant for long periods. Dormant cells represent a real risk for future tumor recurrence, but because they are typically undetectable and insensitive to current modalities of treatment, it is difficult to treat them in time. We describe the metastatic cascade, which is the process that allows tumor cells to detach from the primary tumor, migrate in the tissue, intravasate and extravasate the lymphatics or a blood vessel, adhere to a remote tissue and eventually outgrow. We focus on the critical enabling role of the interactions between tumor cells and immune cells, especially macrophages, in driving the metastatic cascade, and on those stages that can potentially be targeted. In order to prevent the metastatic cascade and tumor recurrence, we would need to target a molecule that is involved in all of the steps of the process, and evidence is brought to suggest that CD147/EMMPRIN is such a protein and that targeting it blocks metastasis and prevents tumor recurrence.

RNA‐binding protein DHX9 promotes glioma growth and tumor‐associated macrophages infiltration via TCF12

“…During in‐depth studies of the tumor microenvironment, TAMs are described as closely related to the occurrence and development of tumors 19,20 . Meanwhile, the infiltration of TAMs is also related to chemokines, such as TGF‐β, IL‐4, IL‐8, and CSF1 21,22 .…”

“…During in-depth studies of the tumor microenvironment, TAMs are described as closely related to the occurrence and development of tumors. 19,20 Meanwhile, the infiltration of TAMs is also related to chemokines, such as TGFβ, IL-4, IL-8, and CSF1. 21,22 Based on these theories, we explored whether DHX9 promoted glioma progression and infiltration of TAMs via regulating the expression of chemokines.…”

Hypoxia‐activated ADCC‐enhanced humanized anti‐CD147 antibody for liver cancer imaging and targeted therapy with improved selectivity

“…Therefore, this hypoxic microenvironment can be capitalized to develop liver cancer‐selective targeted therapies. CD147 is a hub Ag that binds to other proteins (Intergrin, Hyaluronan, CD44, P‐gp/ABCB1, ABCG2, MCT‐1/4, CypA/B, and Gasdermin D) to drive the malignancy of cancer cells 2,3,5,14,26–28,34 . Previous studies revealed that hypoxia induces the upregulation of CD147 in liver cancer cells 35 .…”

“…Cluster of differentiation 147 (CD147) is a highly expressed TAMA that promotes the malignancy of liver cancer through multiple mechanisms. CD147 stimulates the production of matrix metalloproteinases (MMPs) in stromal fibroblasts, endothelial cells, and cancer cells 2,3 . These characteristics make CD147 a new target for Ab targeting.…”

“…CD147 stimulates the production of matrix metalloproteinases (MMPs) in stromal fibroblasts, endothelial cells, and cancer cells. 2 , 3 These characteristics make CD147 a new target for Ab targeting. Metuximab (HAb18) is the first‐generation Ab drug that targets CD147.…”