A Paracrine Loop between Tumor Cells and Macrophages Is Required for Tumor Cell Migration in Mammary Tumors

By J. Wyckoff, Weigang Wang, Elaine Lin, Yarong Wang, F. Pixley, E. Stanley, Thomas Graf, J. Pollard, J. Segall, J. Condeelis. Cancer Research, 2004

1,176 citations recorded by the source corpus.

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.

Subfields: Immunology, Oncology, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/33a1426c78c019e25f9b929c6758eb68a5e6680a

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Citations in the corpus

Molecular mechanisms of invadopodium formation (2005, positive): “This invasion of cancer cells is induced by chemoattractants, such as EGF, that diffuse from blood vessels and get secreted from other cell types, including macrophages (Condeelis and Segall, 2003; Wyckoff et al., 2004).”
Accessories to the crime: functions of cells recruited to the tumor microenvironment. (2012, positive): “EGF promotes invasion/ chemotaxis and intravasation of breast carcinoma cells through a paracrine loop operative between tumor cells and macrophages that are required for mammary cancer cell migration (Wyckoff et al., 2004) via cofilin-dependent actin polymerization (Wang et al., 2007b).”
Macrophages in Tumor Microenvironments and the Progression of Tumors (2012, background): “Subsequently, Wyckoff and colleagues demonstrated a synergistic relationship between breast cancer cells and TAMs in cell migration [67].”
Inflammation, a Key Event in Cancer Development (2006, background): “A paracrine loop of epidermal growth factor might exist for macrophages to synergistically interact with tumors, enhancing metastasis (88).”
Chemotaxis in cancer (2011, background): “In response, cancer cells secrete CSF1, which attracts CSF1 receptor (CSF1R)-expressing TAM”
Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment (2014, background): “Inhibition of CSF-1 or EGF abrogated the migration of both types of cells [80].”
Distinct role of macrophages in different tumor microenvironments. (2006, background): “Experiments conducted in vitro and in vivo indicate that each of these cell types exhibit coordinated movement (14, 53).”
CD4+ T Cells Regulate Pulmonary Metastasis of Mammary Carcinomas by Enhancing Protumor Properties of Macrophages (2009, background): “To determine whether enhanced EGF mRNA expression by TAMs was directly due to IL-4 exposure, we evaluated EGF mRNA expression of TAMs following brief exposure to IL-4, CSF-1, IL-4 plus CSF-1, as compared with pMEC conditioned medium alone, and found that EGF mRNA expression was significantly enhance”
The Tumor Microenvironment Innately Modulates Cancer Progression (2019, background): “, EGF) that promote the movement and invasion of cancer cells (11, 12).”
Matrix metalloproteinases and tumor metastasis (2006, methodology): “Thus, egression of tumor cells into the vasculature have been observed being accompanied by macrophages [59, 148].”
Inhibitory B7-family molecules in the tumour microenvironment (2008, background): “Tumour-associated macrophages markedly outnumber other types of APC, such as DCs, and form an abundant population of APCs in solid tumour”
Macrophage activation by endogenous danger signals (2008, background): “Certainly tumour-derived factors have been considered [143].”