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A distinguishing gene signature shared by tumor-infiltrating Tie2-expressing monocytes, blood “resident” monocytes, and embryonic macrophages suggests common functions and developmental relationships
Open accessAbstract
We previously showed that Tie2-expressing monocytes (TEMs) have nonredundant proangiogenic activity in tumors. Here, we compared the gene expression profile of tumor-infiltrating TEMs with that of tumor-associated macrophages (TAMs), spleen-derived Gr1+Cd11b+ neutrophils/myeloid-derived suppressor cells, circulating “inflammatory” and “resident” monocytes, and tumor-derived endothelial cells (ECs) by quantitative polymerase chain reaction–based gene arrays. TEMs sharply differed from ECs and Gr1+Cd11b+ cells but were highly related to TAMs. Nevertheless, several genes were differentially expressed between TEMs and TAMs, highlighting a TEM signature consistent with enhanced proangiogenic/tissue-remodeling activity and lower proinflammatory activity. We validated these findings in models of oncogenesis and transgenic mice expressing a microRNA-regulated Tie2-GFP reporter. Remarkably, resident monocytes and TEMs on one hand, and inflammatory monocytes and TAMs on the other hand, expressed coordinated gene expression profiles, suggesting that the 2 blood monocyte subsets are committed to distinct extravascular fates in the tumor microenvironment. We further showed that a prominent proportion of embryonic/fetal macrophages, which participate in tissue morphogenesis, expressed distinguishing TEM genes. It is tempting to speculate that Tie2+ embryonic/fetal macrophages, resident blood monocytes, and tumor-infiltrating TEMs represent distinct developmental stages of a TEM lineage committed to execute physiologic proangiogenic and tissue-remodeling programs, which can be coopted by tumors.
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Cites
Mantovani, A., Allavena, P., Sica, A., & Balkwill, F. (2008) · Nature · doi:10.1038/nature07205 · Cited by 11,399
Self-citationMANTOVANI, A., SOZZANI, S., LOCATI, M., ALLAVENA, P., & SICA, A. (2002) · Trends in Immunology · doi:10.1016/s1471-4906(02)02302-5 · Cited by 5,528
Self-citationMonocyte and macrophage heterogeneity
Gordon, S., & Taylor, P. R. (2005) · Nature Reviews Immunology · doi:10.1038/nri1733 · Cited by 5,190
Nahrendorf, M., Swirski, F. K., Aikawa, E., Stangenberg, L., Wurdinger, T., Figueiredo, J.-L., Libby, P., Weissleder, R., & Pittet, M. J. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070885 · Cited by 2,300
Hyaluronan: from extracellular glue to pericellular cue
Toole, B. P. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1391 · Cited by 2,125
The role of myeloid cells in the promotion of tumour angiogenesis
Murdoch, C., Muthana, M., Coffelt, S. B., & Lewis, C. E. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2444 · Cited by 1,642
Trophic macrophages in development and disease
Pollard, J. W. (2009) · Nature Reviews Immunology · doi:10.1038/nri2528 · Cited by 1,178
The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase
Hiratsuka, S., Watanabe, A., Sakurai, Y., Akashi-Takamura, S., Ishibashi, S., Miyake, K., Shibuya, M., Akira, S., Aburatani, H., & Maru, Y. (2008) · Nature Cell Biology · doi:10.1038/ncb1794 · Cited by 642
Brown, B. D., Venneri, M. A., Zingale, A., Sergi, L. S., & Naldini, L. (2006) · Nature Medicine · doi:10.1038/nm1398 · Cited by 484
Self-citationExpression of Tie-2 by Human Monocytes and Their Responses to Angiopoietin-2
Murdoch, C., Tazzyman, S., Webster, S., & Lewis, C. E. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.11.7405 · Cited by 318
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Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm
Biswas, S. K., & Mantovani, A. (2010) · Nature Immunology · doi:10.1038/ni.1937 · Cited by 3,840
Coordinated regulation of myeloid cells by tumours
Gabrilovich, D. I., Ostrand-Rosenberg, S., & Bronte, V. (2012) · Nature Reviews Immunology · doi:10.1038/nri3175 · Cited by 3,544
Zhu, Y., Knolhoff, B. L., Meyer, M. A., Nywening, T. M., West, B. L., Luo, J., Wang-Gillam, A., Goedegebuure, S. P., Linehan, D. C., & DeNardo, D. G. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-3723 · Cited by 1,324
Fantin, A., Vieira, J. M., Gestri, G., Denti, L., Schwarz, Q., Prykhozhij, S., Peri, F., Wilson, S. W., & Ruhrberg, C. (2010) · Blood · doi:10.1182/blood-2009-12-257832 · Cited by 1,153
Macrophage Regulation of Tumor Responses to Anticancer Therapies
De Palma, M., & Lewis, C. E. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.02.013 · Cited by 1,079
Zhou, W., Ke, S. Q., Huang, Z., Flavahan, W., Fang, X., Paul, J., Wu, L., Sloan, A. E., McLendon, R. E., Li, X., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3090 · Cited by 940
Rolny, C., Mazzone, M., Tugues, S., Laoui, D., Johansson, I., Coulon, C., Squadrito, M. L., Segura, I., Li, X., Knevels, E., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2010.11.009 · Cited by 695
Mazzieri, R., Pucci, F., Moi, D., Zonari, E., Ranghetti, A., Berti, A., Politi, L. S., Gentner, B., Brown, J. L., Naldini, L., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.02.005 · Cited by 639
Self-citationTumor-associated macrophages: Functional diversity, clinical significance, and open questions
Biswas, S. K., Allavena, P., & Mantovani, A. (2013) · Seminars in Immunopathology · doi:10.1007/s00281-013-0367-7 · Cited by 551
CCR2 recruits an inflammatory macrophage subpopulation critical for angiogenesis in tissue repair
Willenborg, S., Lucas, T., van Loo, G., Knipper, J. A., Krieg, T., Haase, I., Brachvogel, B., Hammerschmidt, M., Nagy, A., Ferrara, N., et al. (2012) · Blood · doi:10.1182/blood-2012-01-403386 · Cited by 534
The parallel lives of angiogenesis and immunosuppression: cancer and other tales
Motz, G. T., & Coukos, G. (2011) · Nature Reviews Immunology · doi:10.1038/nri3064 · Cited by 481
Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets
Guan, F., Wang, R., Yi, Z., Luo, P., Liu, W., Xie, Y., Liu, Z., Xia, Z., Zhang, H., & Cheng, Q. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02124-y · Cited by 371
Kloepper, J., Riedemann, L., Amoozgar, Z., Seano, G., Susek, K., Yu, V., Dalvie, N., Amelung, R. L., Datta, M., Song, J. W., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1525360113 · Cited by 357
Exploiting and antagonizing microRNA regulation for therapeutic and experimental applications
Brown, B. D., & Naldini, L. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2628 · Cited by 336
Self-citationPinto, A. R., Paolicelli, R., Salimova, E., Gospocic, J., Slonimsky, E., Bilbao-Cortes, D., Godwin, J. W., & Rosenthal, N. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0036814 · Cited by 318
Tumor-Associated Macrophages in Osteosarcoma: From Mechanisms to Therapy
Cersosimo, F., Lonardi, S., Bernardini, G., Telfer, B., Mandelli, G. E., Santucci, A., Vermi, W., & Giurisato, E. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21155207 · Cited by 280
Baer, C., Squadrito, M. L., Laoui, D., Thompson, D., Hansen, S. K., Kiialainen, A., Hoves, S., Ries, C. H., Ooi, C.-H., & De Palma, M. (2016) · Nature Cell Biology · doi:10.1038/ncb3371 · Cited by 259
Coffelt, S. B., Chen, Y.-Y., Muthana, M., Welford, A. F., Tal, A. O., Scholz, A., Plate, K. H., Reiss, Y., Murdoch, C., De Palma, M., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1002802 · Cited by 220
Hollmén, M., Karaman, S., Schwager, S., Lisibach, A., Christiansen, A. J., Maksimow, M., Varga, Z., Jalkanen, S., & Detmar, M. (2016) · OncoImmunology · doi:10.1080/2162402x.2015.1115177 · Cited by 185
Re-Education of Macrophages as a Therapeutic Strategy in Cancer
Kowal, J., Kornete, M., & Joyce, J. A. (2019) · Immunotherapy · doi:10.2217/imt-2018-0156 · Cited by 161
Complement 5a stimulates macrophage polarization and contributes to tumor metastases of colon cancer
Piao, C., Zhang, W.-M., Li, T.-T., Zhang, C.-C., Qiu, S., Liu, Y., Liu, S., Jin, M., Jia, L.-X., Song, W.-C., et al. (2018) · Experimental Cell Research · doi:10.1016/j.yexcr.2018.03.009 · Cited by 106
Cortesi, F., Delfanti, G., Grilli, A., Calcinotto, A., Gorini, F., Pucci, F., Lucianò, R., Grioni, M., Recchia, A., Benigni, F., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.058 · Cited by 100
Self-citationEffects of a synthetic PEG-ylated Tie-2 agonist peptide on endotoxemic lung injury and mortality
David, S., Ghosh, C. C., Kümpers, P., Shushakova, N., Van Slyke, P., Khankin, E. V., Karumanchi, S. A., Dumont, D., & Parikh, S. M. (2011) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00459.2010 · Cited by 96
Im, J. H., Tapmeier, T., Balathasan, L., Gal, A., Yameen, S., Hill, S., Smart, S., Noterdaeme, O., Kelly, M., Brady, M., et al. (2013) · International Journal of Cancer · doi:10.1002/ijc.27677 · Cited by 25
Metadata
- Authors
- Pucci, F., Venneri, M. A., Biziato, D., Nonis, A., Moi, D., Sica, A., Di Serio, C., Naldini, L., & De Palma, M.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2009-07-23
- Volume
- 114
- Issue
- 4
- Pages
- 901-914
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2021955841
- Cited by
- 328
- References
- 11
- FWCI
- 13.24
- Type
- journal article
- Language
- en
- Open access
- bronze
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