Macrophage Biology and Cancer Laboratory, School of Biomedical Sciences, The University of Western Australia, Crawley, WA, Australia.
Front Immunol. 2024 Nov 11;15:1480084. doi: 10.3389/fimmu.2024.1480084. eCollection 2024.
Tumor-associated macrophages (TAMs) recapitulate the developmental and homeostatic behaviors of tissue resident macrophages (TRMs) to promote tumor growth, invasion and metastasis. TRMs arise in the embryo and colonize developing tissues, initially to guide tissue morphogenesis and then to form complex networks in adult tissues to constantly search for threats to homeostasis. The macrophage growth factor, colony-stimulating factor-1 (CSF-1), which is essential for TRM survival and differentiation, is also responsible for the development of the unique motility machinery of mature macrophages that underpins their ramified morphologies, migratory capacity and ability to degrade matrix. Two CSF-1-activated kinases, hematopoietic cell kinase and the p110δ catalytic isoform of phosphatidylinositol 3-kinase, regulate this machinery and selective inhibitors of these proteins completely block macrophage invasion. Considering tumors co-opt the invasive capacity of TAMs to promote their own invasion, these proteins are attractive targets for drug development to inhibit tumor progression to invasion and metastasis.
肿瘤相关巨噬细胞（TAMs）重现了组织驻留巨噬细胞（TRMs）的发育和稳态行为，以促进肿瘤生长、侵袭和转移。TRMs 起源于胚胎并定植于发育中的组织，最初是为了指导组织形态发生，然后在成人组织中形成复杂的网络，以不断寻找对稳态的威胁。巨噬细胞生长因子，集落刺激因子-1（CSF-1），对 TRM 的存活和分化至关重要，也负责成熟巨噬细胞独特的运动机制的发育，这为其分支形态、迁移能力和降解基质的能力提供了基础。两种 CSF-1 激活的激酶，造血细胞激酶和磷脂酰肌醇 3-激酶的 p110δ 催化同工型，调节这种机制，这些蛋白的选择性抑制剂完全阻断巨噬细胞的侵袭。由于肿瘤利用 TAMs 的侵袭能力来促进自身的侵袭，因此这些蛋白是药物开发的有吸引力的靶点，可以抑制肿瘤进展为侵袭和转移。
