The chemokine monocyte chemoattractant protein-1/CCL2 is a promoter of breast cancer metastasis

Abstract

Breast cancer is the most prevalent cancer worldwide, and metastasis is the leading cause of death in cancer patients. Human monocyte chemoattractant protein-1 (MCP-1/CCL2) was isolated from the culture supernatants of not only mitogen-activated peripheral blood mononuclear leukocytes but also malignant glioma cells based on its in vitro chemotactic activity toward human monocytes. MCP-1 was subsequently found to be identical to a previously described tumor cell-derived chemotactic factor thought to be responsible for the accumulation of tumor-associated macrophages (TAMs), and it became a candidate target of clinical intervention; however, the role of TAMs in cancer development was still controversial at the time of the discovery of MCP-1. The in vivo role of MCP-1 in cancer progression was first evaluated by examining human cancer tissues, including breast cancers. Positive correlations between the level of MCP-1 production in tumors and the degree of TAM infiltration and cancer progression were established. The contribution of MCP-1 to the growth of primary tumors and metastasis to the lung, bone, and brain was examined in mouse breast cancer models. The results of these studies strongly suggested that MCP-1 is a promoter of breast cancer metastasis to the lung and brain but not bone. Potential mechanisms of MCP-1 production in the breast cancer microenvironment have also been reported. In the present manuscript, we review studies in which the role of MCP-1 in breast cancer development and progression and the mechanisms of its production were examined and attempt to draw a consensus and discuss the potential use of MCP-1 as a biomarker for diagnosis.

Enzyme-Induced Shape-Shifting Peptide Nanocarrier Coloaded with Paclitaxel and Dipyridamole Inhibits Platelet Function and Tumor Metastasis

“…Macrophage infiltration in breast cancer tumors is associated with tumor progression, metastasis, and poor prognosis . CCL2 is an important factor in tumor-associated macrophage accumulation and a promoter of breast cancer metastasis to the lungs and brain rather than to the bone. − We therefore examined the expression of CCL2 in the lungs of the mice and found a significant decrease in the PD/Pep1 group compared with the other treatment groups, as shown by immunofluorescence (Figure D and Figure S29). It has been shown that the recruitment of inflammatory monocytes for CCR2, the receptor for the chemokine CCL2, and the subsequent recruitment of metastasis-associated macrophages and their interactions with metastatic tumor cells are dependent on CCL2 synthesized in the tumor and stroma .…”

Dysregulation of lncRNA MALAT1 Contributes to Lung Cancer in African Americans by modulating the tumor immune microenvironment

“…It is well accepted that a dynamic and reciprocal relationship develops between cancer cells and components of the TIME that supports cancer cell survival, local invasion, and metastatic dissemination(26). Furthermore, upregulation of MCP-1, a potent monocyte-attracting chemokine, in the TIME could drive cancer development and progression via recruiting M2 macrophages within tumor microenvironment (26). Here we observe a rise in MALAT1 expression, correlating with increased levels of MCP-1 and CD68, CD163, CD206, indicative of M2 macrophages in tumor tissues of AA lung cancer patents.…”

“…Notably, while numerous studies have documented the oncogenic function of MALAT1 in various tumors, its specific role in lung cancer among AAs had not been previously investigated. It is well accepted that a dynamic and reciprocal relationship develops between cancer cells and components of the TIME that supports cancer cell survival, local invasion, and metastatic dissemination(26). Furthermore, upregulation of MCP-1, a potent monocyte-attracting chemokine, in the TIME could drive cancer development and progression via recruiting M2 macrophages within tumor microenvironment (26).…”

“…Notably, while numerous studies have documented the oncogenic function of MALAT1 in various tumors, its specific role in lung cancer among AAs had not been previously investigated. It is well accepted that a dynamic and reciprocal relationship develops between cancer cells and components of the TIME that supports cancer cell survival, local invasion, and metastatic dissemination (26).…”

“…MCP-1 is suggested to influence tumor growth and progression by attracting and activating tumor-associated macrophages within the TIME (26). Given the positive correlation between MALAT1 and MCP-1 levels in tissues, we use immunohistochemistry (IHC) to evaluate macrophage markers (CD68, CD163, CD206, and iNOS), in addition to MCP-1 and KI-67, in the same tissue samples, to correlate these findings with changes in MALAT1.…”