Abstract
Metastasis is responsible for more than 90% of cancer deaths, but remains the least understood stage of tumor progression. The tumor microenvironment contains multiple cells, including nonmalignant and malignant populations. Non-cancer populations are leukocyte infiltration, stromal cells, and vasculature expansion. The dynamic and heterogeneous interactions between cancer cells and tumor microenvironment determine a range of opposite functions of macrophages even within the same type of tumor. Tumor and immune cells secrete growth factors, cytokines, and metabolites that promote TAM pro-tumor polarization. TAMs are primarily considered as pro-inflammatory macrophages producing inflammatory markers such as IL-6 and TNF-α. Also, TAMs can produce reactive oxygen species (ROS) and nitric oxide (NO) that can produce nitrosoperoxycarbonate that results in further inflammation and creates a mutagenic environment for epithelial cells. TAMs are an essential factor in cell-ECM interaction and tumor migration. TAMs are directly involved in the intravasation step by accompanying the tumor cell, producing proteases, and combining TAM-produced EGF and cell-produced CSF-1. Homeostasis and growth of the tumor microenvironment (TME) is regulated by intimate interference in and across all cellular compartments, including malignant cells, endothelial, stromal, and stromal cells. When they begin to proliferate uncontrollably, cancer cells consume large amounts of glucose for bioenergetic, biosynthetic, and antioxidant purposes, often involving the dramatic release of lactate into the environment. TME are capable of secreting high levels of colony-stimulating factor 1 (CSF1). CSF1 and lactate promote M1-type tumor-associated phagocytosis (TAM) re-maximalization into an M2-type immunosuppressive state, characterized by the release of nutritional factors, metabolic modulators, and immunosuppressive molecules that promote disease progression, including.
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Aleebrahim-Dehkordi, E., Deravi, N., Fallahi, M.S., Rezaei, N. (2023). Mechanisms Underlying Tumor-Associated Macrophages (TAMs)-Facilitated Metastasis. In: Rezaei, N. (eds) Handbook of Cancer and Immunology. Springer, Cham. https://doi.org/10.1007/978-3-030-80962-1_66-1
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