Integrins, a group of transmembrane receptors, play a crucial role in mediating the interactions between cells and extracellular matrix (ECM) proteins. The intracellular signaling initiated by these cell-matrix interactions in leukocytes mediates many essential cellular processes such as survival, migration, metabolism, and other immunological functions. Macrophages, as phagocytes, participate in both proinflammatory and anti-inflammatory processes, including progression. Numerous reports have shown that the integrin-regulated secretome, comprising cytokines, chemokines, growth factors, proteases, and other bioactive molecules, is a crucial modulator of macrophage functions in tumors, significantly influencing macrophage programming and reprogramming within the tumor microenvironment (TME) in addition to driving their step-by-step entry process into tumor tissue spaces. Importantly, studies have demonstrated a pivotal role for integrin receptor-mediated secretome and associated signaling pathways in functional reprogramming from anti-tumorigenic to pro-tumorigenic phenotype in tumor-associated macrophages (TAMs). In this comprehensive review, we have provided an in-depth analysis of the latest findings of various key pathways, mediators, and signaling cascades associated with integrin-driven polarization of macrophages in tumors. This manuscript will provide an updated understanding of the modulation of inflammatory monocytes/ macrophages and TAMs by integrin-driven secretory pathways in various functions such as migration, differentiation, and their role in tumor progression, angiogenesis, and metastasis.

中文翻译：

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整合素和整合素驱动的分泌通路作为肿瘤微环境中肿瘤相关巨噬细胞募集和重编程的多维调节因子


整合素是一组跨膜受体，在介导细胞与细胞外基质 （ECM） 蛋白之间的相互作用中起着至关重要的作用。白细胞中这些细胞-基质相互作用引发的细胞内信号转导介导许多重要的细胞过程，例如存活、迁移、代谢和其他免疫功能。巨噬细胞作为吞噬细胞，参与促炎和抗炎过程，包括进展。大量报告表明，整合素调节的分泌组，包括细胞因子、趋化因子、生长因子、蛋白酶和其他生物活性分子，是肿瘤中巨噬细胞功能的关键调节剂，除了驱动巨噬细胞逐步进入肿瘤组织空间外，还显着影响肿瘤微环境 （TME） 内的巨噬细胞编程和重编程。重要的是，研究表明，整合素受体介导的分泌组和相关信号通路在肿瘤相关巨噬细胞 （TAM） 中从抗肿瘤表型到促肿瘤表型的功能重编程中起着关键作用。在这篇全面的综述中，我们对与肿瘤中巨噬细胞整合素驱动的极化相关的各种关键途径、介质和信号级联的最新发现进行了深入分析。本手稿将提供对整合素驱动的分泌途径在迁移、分化等各种功能中对炎性单核细胞/巨噬细胞和 TAM 的调节的最新理解，以及它们在肿瘤进展、血管生成和转移中的作用。