High Levels of BMP2 Promote Liver Cancer Growth via the Activation of Myeloid-Derived Suppressor Cells
Open accessAbstract
Bone morphogenetic protein 2(BMP2) signaling had significant roles in diverse pathological process, such as cancer. Nevertheless, the interaction between BMP2 and carcinoma development remained largely unknown. Particularly, roles of BMP2 playing in the development of liver cancer remained controversial，and mechanisms were unclear. BMP2 with strong osteogenic potential had been manufactured into various bone materials. However, cancer risk concerns raised in recent years. Thus, we focused on analyzing the effects of exogenous BMP2 on the growth of liver cancer and the detailed mechanisms. We found that both intravenous injection of rhBMP2 and in vivo implantation of rhBMP2 materials could lead to the expansion of myeloid-derived suppressor cells (MDSCs) in peripheral blood, and subsequently enhanced the infiltration of MDSCs into tumor in vivo. Furthermore, BMP2 signaling activated MDSCs could secret IL6 to enhance cell proliferation of liver cancer cells in vitro and facilitate liver cancer growth in vivo. Our study indicated that increased concentration of BMP2 within the peripheral blood could enhance liver cancer growth via the activation of MDSCs. In this study, roles of BMP2 playing in liver cancer growth were further confirmed and the detailed mechanisms about how BMP2 enhanced the liver cancer growth were also elucidated.
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BMP-2 has known roles in development, tumorigenesis, and various body tissues.
“BMP-2 has known roles in development [36], on tumorigenesis, [37] and in various body tissues [38–40].”
From Keratin Scaffold Formulation Impacts rhBMP-2 Biodistribution and Bone Regeneration in a Rat Femur Defect Model (2025) · cites this paper as [37]
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Cites
Myeloid-derived-suppressor cells as regulators of the immune system
Gabrilovich, D. I., & Nagaraj, S. (2009) · Nature Reviews Immunology · doi:10.1038/nri2506 · Cited by 6,753 · see citing works
Bone: Formation by Autoinduction
Urist, M. R. (1965) · Science · doi:10.1126/science.150.3698.893 · Cited by 5,529 · see citing works
The Nature of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment
Kumar, V., Patel, S., Tcyganov, E., & Gabrilovich, D. I. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.01.004 · Cited by 2,008 · see citing works
Wu, M., Chen, G., & Li, Y. (2016) · Bone Research · doi:10.1038/boneres.2016.9 · Cited by 1,612 · see citing works
Satoh, T., Takeuchi, O., Vandenbon, A., Yasuda, K., Tanaka, Y., Kumagai, Y., Miyake, T., Matsushita, K., Okazaki, T., Saitoh, T., et al. (2010) · Nature Immunology · doi:10.1038/ni.1920 · Cited by 1,156 · see citing works
History of myeloid-derived suppressor cells
Talmadge, J. E., & Gabrilovich, D. I. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3581 · Cited by 1,148 · see citing works
Roessler, S. K., Jia, H.-L., Budhu, A., Forgues, M., Ye, Q.-H., Lee, J., Thorgeirsson, S. S., Sun, Z., Tang, Z., Qin, L., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-2607 · Cited by 1,047 · see citing works
Signaling cross-talk between TGF-β/BMP and other pathways
Guo, X., & Wang, X. (2008) · Cell Research · doi:10.1038/cr.2008.302 · Cited by 1,027 · see citing works
Myeloid-Derived Suppressor Cells Inhibit T-Cell Activation by Depleting Cystine and Cysteine
Srivastava, M. K., Sinha, P., Clements, V. K., Rodrı́guez, P. C., & Ostrand‐Rosenberg, S. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-2587 · Cited by 954 · see citing works
BMP receptor signaling: Transcriptional targets, regulation of signals, and signaling cross-talk
Miyazono, K., Maeda, S., & Imamura, T. (2005) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2005.01.009 · Cited by 888 · see citing works
Menyhárt, O., Nagy, Á., & Győrffy, B. (2018) · Royal Society Open Science · doi:10.1098/rsos.181006 · Cited by 507 · see citing works
Schlecker, E., Stojanovic, A., Eisen, C., Quack, C., Falk, C. S., Umansky, V., & Cerwenka, A. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1201018 · Cited by 439 · see citing works
Complications with the use of bone morphogenetic protein 2 (BMP-2) in spine surgery
Tannoury, C. A., & An, H. S. (2014) · The Spine Journal · doi:10.1016/j.spinee.2013.08.060 · Cited by 434 · see citing works
Balancing BMP Signaling through Integrated Inputs into the Smad1 Linker
Sapkota, G. P., Alarcón, C. R., Spagnoli, F. M., Brivanlou, A. H., & Massagué, J. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.01.006 · Cited by 419 · see citing works
Otsuji, M., Kimura, Y., Aoe, T., Okamoto, Y., & Saito, T. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.23.13119 · Cited by 338 · see citing works
Chen, Z., Wu, C., Gu, W., Klein, T. J., Crawford, R., & Xiao, Y. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.11.014 · Cited by 324 · see citing works
Peng, D., Tanikawa, T., Li, W., Zhao, L., Vatan, L., Szeliga, W., Wan, S., Wei, S., Wang, Y., Liu, Y., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-2528 · Cited by 274 · see citing works
Liver cancer epidemic in China: Past, present and future
Chen, J., & Zhang, S. (2010) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2010.11.002 · Cited by 248 · see citing works
Myeloid-Derived Suppressor Cells in Human Cancer
Nagaraj, S., & Gabrilovich, D. I. (2010) · The Cancer Journal · doi:10.1097/ppo.0b013e3181eb3358 · Cited by 222 · see citing works
Lombardo, Y., Scopelliti, A., Cammareri, P., Todaro, M., Iovino, F., Ricci–Vitiani, L., Gulotta, G., Dieli, F., de Maria, R., & Stassi, G. (2011) · Gastroenterology · doi:10.1053/j.gastro.2010.10.005 · Cited by 222 · see citing works
Bone Morphogenetic Protein 7 in the Development and Treatment of Bone Metastases from Breast Cancer
Buijs, J. T., Henriquez, N. V., van Overveld, P. G. M., van der Horst, G., Que, I., Schwaninger, R., Rentsch, C. A., ten Dijke, P., Cleton-Jansen, A., Driouch, K., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-2490 · Cited by 205 · see citing works
Signaling pathways involved in MDSC regulation
Trikha, P., & Carson, W. E. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.04.003 · Cited by 201 · see citing works
The Immunomodulatory Role of BMP-2 on Macrophages to Accelerate Osteogenesis
Wei, F., Zhou, Y., Wang, J., Liu, C., & Xiao, Y. (2017) · Tissue Engineering Part A · doi:10.1089/ten.tea.2017.0232 · Cited by 147 · see citing works
Buijs, J. T., van der Horst, G., van den Hoogen, C., Cheung, H., de Rooij, B., Kroon, J., Petersen, M., van Overveld, P. G. M., Pelger, R. C. M., & van der Pluijm, G. (2011) · Oncogene · doi:10.1038/onc.2011.400 · Cited by 144 · see citing works
Kodach, L. L., Jacobs, R. J., Voorneveld, P. W., Wildenberg, M. E., Verspaget, H. W., van Wezel, T., Morreau, H. M., Hommes, D. W., Peppelenbosch, M. P., BRINK, G. R. V. D., et al. (2011) · Gut · doi:10.1136/gut.2011.237495 · Cited by 142 · see citing works
Diverse Biological Effect and Smad Signaling of Bone Morphogenetic Protein 7 in Prostate Tumor Cells
Yang, S., Zhong, C., Frenkel, B., Reddi, A. H., & Roy‐Burman, P. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-0289 · Cited by 136 · see citing works
Alarmo, E., Kuukasjärvi, T., Karhu, R., & Kallioniemi, A. H. (2006) · Breast Cancer Research and Treatment · doi:10.1007/s10549-006-9362-1 · Cited by 118 · see citing works
Mechanisms of action of bone morphogenetic proteins in cancer
Belnoue-Davis, H. L., Raja, E., Miyazono, K., Tsubakihara, Y., & Moustakas, A. (2015) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2015.11.009 · Cited by 96 · see citing works
Lee, Y., Schwarz, E. M., Davies, M., Jo, M., Gates, J. J., Wu, J., Zhang, X., & Lieberman, J. R. (2002) · Journal of Orthopaedic Research® · doi:10.1016/s0736-0266(02)00095-5 · Cited by 95 · see citing works
Lee, J., Lee, G. T., Woo, S. H., Ha, Y., Kwon, S. J., Kim, W., & Kim, I. Y. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-4563 · Cited by 87 · see citing works
Association Between BMP-2 and Carcinogenicity
Skovrlj, B., Koehler, S. M., Anderson, P. A., Qureshi, S. A., Hecht, A. C., Iatridis, J. C., & Cho, S. K.-W. (2015) · Spine · doi:10.1097/brs.0000000000001126 · Cited by 83 · see citing works
Pouliot, F., Blais, A., & Labrie, C. (2003) · PubMed · Cited by 82 · see citing works
Hsu, Y., Huang, M., Yang, C., Hung, J., Wu, L., & Kuo, P. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.256156 · Cited by 77 · see citing works
Expression of bone morphogenetic protein 2 in breast cancer cells inhibits hypoxic cell death
Raida, M. K., Clement, J. H., Ameri, K., Cheng, H., Leek, R., & Harris, A. L. (2005) · International Journal of Oncology · doi:10.3892/ijo.26.6.1465 · Cited by 61 · see citing works
BMP-2 induces motility and invasiveness by promoting colon cancer stemness through STAT3 activation
Kim, B. R., Oh, S. C., Lee, D.-H., Kim, J. L., Lee, S. Y., Kang, M. H., Lee, S. I., Kang, S., Joung, S. Y., & Min, B. W. (2015) · Tumor Biology · doi:10.1007/s13277-015-3681-y · Cited by 55 · see citing works
A Novel Bone Morphogenetic Protein Signaling in Heterotypic Cell Interactions in Prostate Cancer
Yang, S., Pham, L. K., Liao, C., Frenkel, B., Reddi, A. H., & Roy‐Burman, P. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-5074 · Cited by 55 · see citing works
Myeloid-derived suppressor cells in mammary tumor progression in FVB Neu transgenic mice
Abe, F., Dafferner, A. J., Donkor, M. K., Westphal, S. N., Scholar, E. M., Solheim, J. C., Singh, R. K., Hoke, T. A., & Talmadge, J. E. (2009) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-009-0719-2 · Cited by 53 · see citing works
Langenfeld, E. M., Hong, C. C., Lanke, G., & Langenfeld, J. E. (2013) · PLoS ONE · doi:10.1371/journal.pone.0061256 · Cited by 51 · see citing works
Development of an in vitro model to study the impact of BMP-2 on metastasis to bone
Kwon, H., Kim, H. J., Rice, W. L., Subramanian, B., Park, S., Georgakoudi, I., & Kaplan, D. L. (2010) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.268 · Cited by 49 · see citing works
miR-656 inhibits glioma tumorigenesis through repression of BMPR1A
Guo, M., Jiang, Z., Zhang, X., Deng, L., Ha, A. D., Sun, J., Du, W., Wu, Z., Hu, L., Khadarian, K. A., et al. (2014) · Carcinogenesis · doi:10.1093/carcin/bgu030 · Cited by 45 · see citing works
BMP Signaling Promotes the Growth of Primary Human Colon Carcinomas in vivo
Lorente‐Trigos, A., Varnat, F., Melotti, A., & Altaba, A. R. I. (2010) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjq035 · Cited by 45 · see citing works
Zheng, Y., Wang, X., Wang, H., Yan, W., Zhang, Q., & Chang, X. (2014) · Tumor Biology · doi:10.1007/s13277-014-1673-y · Cited by 38 · see citing works
Xu, Z., Li, L., Qian, Y., Song, Y., Qin, L., Duan, Y., Wang, Μ., Li, P., Jiang, B., Ma, C., et al. (2019) · Oncogene · doi:10.1038/s41388-019-0847-x · Cited by 33 · see citing works
Beck, C., Schreiber, K., Schreiber, H. W., & Rowley, D. A. (2002) · European Journal of Immunology · doi:10.1002/immu.200390003 · Cited by 24 · see citing works
Wu, J.-B., Fu, H.-Q., Huang, L.-Z., Liu, A.-W., & Zhang, J.-X. (2010) · Cancer Gene Therapy · doi:10.1038/cgt.2010.55 · Cited by 23 · see citing works
Lee, J. H., Lee, E.-N., & Nam, S. H. (2013) · Drug and Chemical Toxicology · doi:10.3109/01480545.2013.806530 · Cited by 13 · see citing works
Yoon, B.-H., Lee, J. H., Na, K., Cho, J., & Choe, S. (2015) · Regulatory Toxicology and Pharmacology · doi:10.1016/j.yrtph.2015.06.007 · Cited by 8 · see citing works
The Effects of rhBMP-2 on Human Osteosarcoma Cells and Human Gingival FibroblastsINVITRO
Murphy, M. G., Mailhot, J. M., Borke, J. L., Wataha, J. C., Sharawy, M., & Smith, A. (2001) · Journal of Oral Implantology · doi:10.1563/1548-1336(2001)027 · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Benedetti, F., Curreli, S., & Zella, D. (2020) · Microorganisms · doi:10.3390/microorganisms8091351 · Cited by 75 · see citing works
BMP2 as a promising anticancer approach: functions and molecular mechanisms
Li, T., Lai, Y.-W., Han, X., Niu, X., & Zhang, P.-X. (2022) · Investigational New Drugs · doi:10.1007/s10637-022-01298-4 · Cited by 23 · see citing works
Emerging Roles for Browning of White Adipose Tissue in Prostate Cancer Malignant Behaviour
Álvarez-Artime, A., García-Soler, B., Sainz, R. M., & Mayo, J. C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115560 · Cited by 21 · see citing works
Chernysheva, M., Ruchko, E. S., & Валерьевич, Е. А. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262110723 · Cited by 20 · see citing works
Mechanism and function of miR-140 in human cancers: A review and in silico study
Taheri, F., Ebrahimi, S. O., Heidari, R., pour, S. N., & Reiisi, S. (2022) · Pathology - Research and Practice · doi:10.1016/j.prp.2022.154265 · Cited by 12 · see citing works
Kalds, P., Huang, S., Chen, Y., & Wang, X. (2022) · Communications Biology · doi:10.1038/s42003-022-04199-7 · Cited by 12 · see citing works
Self-citationKalal, A. A., & Mohapatra, S. (2025) · Current Issues in Molecular Biology · doi:10.3390/cimb47030156 · Cited by 9 · see citing works
Afaloniati, H., Poutahidis, T., Giakoustidis, A. E., Gargavanis, A. A., Giakoustidis, D. E., & Angelopoulou, K. (2021) · Molecular Biology Reports · doi:10.1007/s11033-020-06089-9 · Cited by 6 · see citing works
Liao, J., Liu, Q., Chen, J., Lu, Z., Mo, H., & Jia, J. H. (2022) · Proteome Science · doi:10.1186/s12953-022-00192-4 · Cited by 5 · see citing works
Wu, H., Xu, Y., Gong, Y. Y., Huntriss, J., & Routledge, M. N. (2024) · Mutagenesis · doi:10.1093/mutage/geae005 · Cited by 5 · see citing works
TGF-β Promotes Hepatocellular Carcinoma Metastasis Through Through m6A Modification of PCDHGA9
Wang, H., GUAN, W., Zhang, X., Wu, Y., Ou, Y., ZHANG, Y., Zeng, Z., & Yao, H. (2024) · Cancer Biotherapy and Radiopharmaceuticals · doi:10.1089/cbr.2023.0144 · Cited by 5 · see citing works
Targeting BMP2 for therapeutic strategies against hepatocellular carcinoma
Li, P., Shang, Y., Yuan, L., Tong, J., & Chen, Q. (2024) · Translational Oncology · doi:10.1016/j.tranon.2024.101970 · Cited by 4 · see citing works
Zhong, Q., Wang, Z., Kang, H., & Wu, R. (2022) · Pathology - Research and Practice · doi:10.1016/j.prp.2022.154056 · Cited by 4 · see citing works
Jiang, D., Xu, S., Zhang, C., Hu, C., Li, L., Zhang, M., Wu, H., Yang, D., & Liu, Y. (2023) · Oncology Letters · doi:10.3892/ol.2023.13842 · Cited by 4 · see citing works
Saul, J. M., Bohnert, J. S., O’Brien, M., Alnuaimi, S., Carnwath, T. P., Dunivan, Q., Coffin, D. W., & Smith, T. L. (2025) · Tissue Engineering and Regenerative Medicine · doi:10.1007/s13770-025-00747-4 · Cited by 3 · see citing works
“BMP-2 has known roles in development [36], on tumorigenesis, [37] and in various body tissues [38–40].”
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Chen, J., Qiu, J., Zhang, W., Nie, Z., Gao, X., Xu, G., Kang, L., & Zhang, Z. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1619194 · Cited by 1 · see citing works
Wang, M., Song, Z., Yuan, H., Liu, C., Wang, W., Yang, N., Sun, K., Zhang, S., Qin, X., Li, J., et al. (2025) · Cancer Research · doi:10.1158/0008-5472.can-24-4392 · Cited by 1 · see citing works
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Peng, H., Liu, Y., & Song, Z. (2023) · PubMed Central · doi:10.11817/j.issn.1672-7347.2023.230077
Liao, J., Liu, Q., Chen, J., Lu, Z., Mo, H., & Jia, J. (2022) · Figshare · doi:10.6084/m9.figshare.20131328
Liao, J., Liu, Q., Chen, J., Lu, Z., Mo, H., & Jia, J. (2022) · Figshare · doi:10.6084/m9.figshare.20131325
Liao, J., Liu, Q., Chen, J., Lu, Z., Mo, H., & Jia, J. (2022) · Figshare · doi:10.6084/m9.figshare.20131322
- Authors
- Wu, G., Huang, F., Chen, Y., Zhuang, Y., Huang, Y., & Xie, Y.
- Affiliations
- Fujian Medical University (CN)
- First Affiliated Hospital of Fujian Medical University (CN)
- Corresponding author
- Wu, Gui
- Xie, Yun
- Venue
- Frontiers in Oncology
- Publisher
- Frontiers Media SA
- Published
- 2020-03-04
- Volume
- 10
- Pages
- 194-194
- ISSN
- 2234-943X (ISSN-L)
- PMC
- PMC7064622
- OpenAlex
- W3009852575
- Cited by
- 22
- References
- 48
- Citations by year
- 2025: 5 · 2024: 3 · 2023: 2 · 2022: 9 · 2021: 2 · 2020: 1
- FWCI
- 1.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Oncology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- BMP-2, liver cancer, hepatocellular carcinoma, myeloid-derived suppressor cells, tumor growth, interleukin-6, tumor cell proliferation, tumor microenvironment
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