A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors
A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors
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DOI：
10.1158/0008-5472.can-04-1449
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发表时间：
2004-10-01
期刊：
影响因子：
11.2
通讯作者：
Condeelis, J
中科院分区：
文献类型：
--
作者：
Wyckoff, J;Wang, WG;Condeelis, J
肿瘤细胞侵入周围结缔组织和血管是乳腺肿瘤转移扩散的关键步骤。尽管原发性肿瘤中巨噬细胞的存在与转移潜力的增加有关，但这一观察结果的机制基础尚不清楚。使用基于趋化性的体内侵袭试验和基于多光子的活体成像，我们表明巨噬细胞和肿瘤细胞之间的相互作用促进了原发性肿瘤中癌细胞的迁移。表皮生长因子（EGF）或集落刺激因子1（CSF-1）的梯度刺激肿瘤细胞和巨噬细胞聚集到微针中，尽管肿瘤细胞仅表达EGF受体，巨噬细胞仅表达CSF-1受体。活体成像显示巨噬细胞和肿瘤细胞向含有EGF或CSF-1的微针迁移。抑制CSF-1或EGF刺激的信号传导减少了两种细胞类型的迁移。这项工作提供了第一个直接的证据，巨噬细胞和肿瘤细胞之间的协同作用，在体内细胞迁移过程中，并表明巨噬细胞如何可能有助于转移的机制。
Invasion of tumor cells into the surrounding connective tissue and blood vessels is a key step in the metastatic spread of breast tumors. Although the presence of macrophages in primary tumors is associated with increased metastatic potential, the mechanistic basis for this observation is unknown. Using a chemotaxis-based in vivo invasion assay and multiphoton-based intravital imaging, we show that the interaction between macrophages and tumor cells facilitates the migration of carcinoma cells in the primary tumor. Gradients of either epidermal growth factor (EGF) or colony-stimulating factor 1 (CSF-1) stimulate collection into microneedles of tumor cells and macrophages even though tumor cells express only EGF receptor and macrophages express only CSF-1 receptor. Intravital imaging shows that macrophages and tumor cells migrate toward microneedles containing either EGF or CSF-1. Inhibition of either CSF-1- or EGF-stimulated signaling reduces the migration of both cell types. This work provides the first direct evidence for a synergistic interaction between macrophages and tumor cells during cell migration in vivo and indicates a mechanism for how macrophages may contribute to metastasis.