FLT1 signaling in metastasis-associated macrophages activates an inflammatory signature that promotes breast cancer metastasis

Qian, Bin‐Zhi; Zhang, Hui; Li, Jiufeng; He, Tianfang; Yeo, Eun-Jin; Soong, Daniel; Carragher, Neil O.; Munro, Alison; Chang, Alvin; Bresnick, Anne R.; Lang, Richard A.; Pollard, Jeffrey W.

doi:10.1083/jcb.2104oia168

Cited by 40 publications

(58 citation statements)

References 18 publications

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“…This re-enforces our data showing B20-4.1.1 inhibits VEGF120-dependent processes predominantly in the subcutaneous primary tumor for its antimetastatic effect, as well as re-enforcing a role for VEGF120 expression in conferring fibrosarcoma cells with additional advantages during the early stages of survival within the tissue of the lung that are not sensitive to anti-VEGFA therapy. As our data show, there is a high degree of redundancy in VEGFR1 ligands in mice with VEGF120-expressing tumors, particularly in plasma and lung tissue, hence targeting VEGFR1 directly may inhibit survival of disseminated cells within the lung, as found in previous studies of other tumor types (39,40). In a pilot study, we found that treatment with the VEGFR1/2 tyrosine kinase inhibitor cediranib tended to decrease survival of fs120-LS cells within the lung 48 hours after intravenous injection but this effect was not statistically significant ( Supplementary Fig.…”

Section: Discussionsupporting

confidence: 74%

Differential Expression of VEGFA Isoforms Regulates Metastasis and Response to Anti-VEGFA Therapy in Sarcoma

et al. 2017

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Elevated plasma concentrations of soluble VEGFA isoforms are associated with poor prognosis in parallel with improved response to treatment with the anti-VEGFA antibody bevacizumab. To uncover the underlying mechanism to these observations, we administered anti-VEGFA therapy to mice bearing luminescent mouse fibrosarcomas expressing single VEGFA isoforms or their wild-type counterparts expressing all isoforms (fs120, fs164, fs188, or fsWT). Expression of the more soluble isoforms conferred an advantage for lung metastasis from subcutaneous tumors (fs120/164 vs. fs188/WT); fs120 cells also produced more lung colonies than fs188 cells when injected intravenously. Metastasis from subcutaneous fs120 tumors was more sensitive than fs188 to treatment with the anti-VEGFA antibody B20-4.1.1. Despite elevated plasma levels of VEGFA in fs120 tumor-bearing mice and a dependence on VEGF receptor 1 activity for metastasis to the lung, B20-4

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Section: Discussionsupporting

confidence: 74%

Differential Expression of VEGFA Isoforms Regulates Metastasis and Response to Anti-VEGFA Therapy in Sarcoma

et al. 2017

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“…Breast cancer cells survive poorly in isolation and participate in a complex relationship with surrounding stromal and immune cells in the tumor microenvironment which can support tumor cell survival, proliferation and spreading to other organs (17,20,21,36,39). CAFs and TAMs are the most abundant stromal cells in solid cancers, including breast cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Macrophages can be polarized into M1-like anti-tumorigenic macrophages and M2-like pro-tumorigenic macrophages (14)(15)(16). M2-like macrophages can influence tumor initiation, progression, metastasis (17)(18)(19) and resistance to therapies (20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Blockade of insulin-like growth factors increases efficacy of paclitaxel in metastatic breast cancer

Ireland

Santos

Campbell

et al. 2017

Preprint

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Running titleStromal IGF regulates breast cancer metastasis not peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was . http://dx.doi.org/10.1101/165068 doi: bioRxiv preprint first posted online Jul. 23, 2017; 2 Word count: 3,818 words -(excluding abstract, references and figure legends). ABSTRACTBreast cancer remains the leading cause of cancer death in women due to metastasis and the development of resistance to established therapies.Macrophages are the most abundant immune cells in the breast tumor microenvironment and can both inhibit and support cancer progression. Thus, gaining a better understanding of how macrophages support cancer could lead to the development of more effective therapies. In this study, we find that breast cancer associated macrophages express high levels of insulin-like growth factors 1 and 2 (IGFs) and are the main source of IGFs within both primary and metastatic tumours.

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“…First, Bin-Zhi Qian (University of Edinburgh, UK) discussed the mononuclear phagocyte system and its role in breast cancer metastasis, where they have previously shown the importance of host macrophages for lung metastasis [29,30]. Dr Qian focused on breast cancer bone metastasis, where they found that the CCL2/CCR2 axis was critical in recruiting macrophages derived from circulating inflammatory monocytes.…”

Section: Modeling Metastasismentioning

confidence: 99%

EACR-MRS conference on Seed and Soil: In Vivo Models of Metastasis

Alves

Cohen

Ersan

et al. 2017

Clin Exp Metastasis

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New experimental tools are urgently required to better understand the metastatic process. The importance of such tools is underscored by the fact that many anti-cancer therapies are generally ineffective against established metastases. This makes a major contribution to the fact that metastatic spread is responsible for over 90% of cancer patient deaths. It was therefore timely that the recent "Seed and Soil: In Vivo Models of Metastasis" conference held in Berlin, Germany (27-29 of November 2017) aimed to give an in-depth overview of the latest research models and tools for studying metastasis, and to showcase recent findings from world-leading metastasis researchers. This Meeting Report summarises the major themes of this ground-breaking conference.

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FLT1 signaling in metastasis-associated macrophages activates an inflammatory signature that promotes breast cancer metastasis

Cited by 40 publications

References 18 publications

Differential Expression of VEGFA Isoforms Regulates Metastasis and Response to Anti-VEGFA Therapy in Sarcoma

Differential Expression of VEGFA Isoforms Regulates Metastasis and Response to Anti-VEGFA Therapy in Sarcoma

Blockade of insulin-like growth factors increases efficacy of paclitaxel in metastatic breast cancer

EACR-MRS conference on Seed and Soil: In Vivo Models of Metastasis

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