Skip to main content
SpringerLink
Log in

M2 Macrophage-Derived Exosomal Ferritin Heavy Chain Promotes Colon Cancer Cell Proliferation

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Colon cancer is a widespread life-threatening malignancy with complex and multifactorial etiology. Both epidemiological cohort studies and basic research support the substantial role of iron metabolism in colon cancer. Thus, understanding the mechanisms of how essential iron metabolic proteins are dysregulated may provide new treatment strategies for colon cancer. Ferritin is the main iron storage protein that occupies a vital position in iron metabolism. Studies reported that ferritin is differentially highly expressed in tissues from multiple malignancies. However, the source and function of highly expressed ferritin in colon cancer have not been explored. In this study, we found that the protein level but not RNA level of ferritin heavy chain (FTH1) was upregulated in colon cancer using paired clinical samples. Co-culture system was used to mimic the in vivo circumstance and study the cell–cell communication of macrophages and colon cancer cells. Results showed that M2 macrophages could substantially increase the FTH1 levels in colon cancer cells. This effect could be blocked by the exosome biogenesis/ secretion inhibitor GW4869, implying the vital role of exosomes in this biological process. Besides, we found that purified exosomes from M2 macrophages could deliver FTH1 into colon cancer cells and promote cell proliferation. Furtherly, EdU assay and live cell imaging system were performed in FTH1-OE (overexpression) colon cancer cell lines and confirmed the cell proliferation promoting effect of FTH1. Our results unveil the source and function of highly expressed FTH1 in colon cancer and provide a new potential therapeutic target for the treatment of colon cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

FTH1:

Ferritin heavy chain 1

OE:

Overexpression

DMT1:

Divalent metal transporter1

FTL:

Ferritin light chain

TME:

Tumor microenvironment

TAMs:

Tumor-associated macrophages

COAD:

Colonic adenocarcinoma

IHC:

Immunohistochemistry

RT-qPCR:

Reverse transcription-quantitative polymerase chain reaction

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

GEPIA:

Gene Expression Profiling Interactive Analysis

TCGA:

The Cancer Genome Atlas

GTEx:

Genotype-Tissue Expression

FBS:

Fetal bovine serum

PMA:

Phorbol-12-myristate-13-acetate

CM:

Conditioned medium

HRP:

Horseradish Peroxidase

NTA:

Nanoparticle Tracking Analysis

DAPI:

4′,6-Diamidino-2-phenylindole

TPM:

Transcripts per million

iNOS:

Induced nitrogen monoxide synthase

ARG1:

Arginase-1

LIP:

Labile iron pools

References

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71(3):209–249. https://doi.org/10.3322/caac.21660

    Article  PubMed  Google Scholar 

  2. Loomans-Kropp HA, Umar A (2019) Increasing incidence of colorectal cancer in young adults. J Cancer Epidemiol 2019:9841295. https://doi.org/10.1155/2019/9841295

    Article  PubMed  PubMed Central  Google Scholar 

  3. Juloski JT, Rakic A, Cuk VV, Cuk VM, Stefanovic S, Nikolic D, Jankovic S, Trbovich AM, De Luka SR (2020) Colorectal cancer and trace elements alteration. J Trace Elem Med Biol 59:126451. https://doi.org/10.1016/j.jtemb.2020.126451

    Article  CAS  PubMed  Google Scholar 

  4. Feyzi A, Delkhosh A, Nasrabadi HT, Cheraghi O, Khakpour M, Barekati-Mowahed M, Soltani S, Mohammadi SM, Kazemi M, Hassanpour M, Rezabakhsh A, Maleki-Dizaji N, Rahbarghazi R, Namdarian R (2017) Copper sulfate pentahydrate reduced epithelial cytotoxicity induced by lipopolysaccharide from enterogenic bacteria. Biomed Pharmacother 89:454–461. https://doi.org/10.1016/j.biopha.2017.02.060

    Article  CAS  PubMed  Google Scholar 

  5. Cross AJ, Leitzmann MF, Gail MH, Hollenbeck AR, Schatzkin A, Sinha R (2007) A prospective study of red and processed meat intake in relation to cancer risk. PLoS Med 4(12):e325. https://doi.org/10.1371/journal.pmed.0040325

    Article  PubMed  PubMed Central  Google Scholar 

  6. Cross AJ, Ferrucci LM, Risch A, Graubard BI, Ward MH, Park Y, Hollenbeck AR, Schatzkin A, Sinha R (2010) A large prospective study of meat consumption and colorectal cancer risk: an investigation of potential mechanisms underlying this association. Cancer Res 70(6):2406–2414. https://doi.org/10.1158/0008-5472.CAN-09-3929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Zhu CS, Pinsky PF, Kramer BS, Prorok PC, Purdue MP, Berg CD, Gohagan JK (2013) The prostate, lung, colorectal, and ovarian cancer screening trial and its associated research resource. J Natl Cancer Inst 105(22):1684–1693. https://doi.org/10.1093/jnci/djt281

    Article  PubMed  PubMed Central  Google Scholar 

  8. Abbaspour N, Hurrell R, Kelishadi R (2014) Review on iron and its importance for human health. J Res Med Sci 19(2):164–174

    PubMed  PubMed Central  Google Scholar 

  9. Torti SV, Manz DH, Paul BT, Blanchette-Farra N, Torti FM (2018) Iron and cancer. Annu Rev Nutr 38:97–125. https://doi.org/10.1146/annurev-nutr-082117-051732

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Xue X, Ramakrishnan SK, Weisz K, Triner D, Xie L, Attili D, Pant A, Gyorffy B, Zhan M, Carter-Su C, Hardiman KM, Wang TD, Dame MK, Varani J, Brenner D, Fearon ER, Shah YM (2016) Iron uptake via DMT1 integrates cell cycle with JAK-STAT3 signaling to promote colorectal tumorigenesis. Cell Metab 24(3):447–461. https://doi.org/10.1016/j.cmet.2016.07.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ren Y, Walczyk T (2014) Quantification of ferritin bound iron in human serum using species-specific isotope dilution mass spectrometry. Metallomics 6(9):1709–1717. https://doi.org/10.1039/c4mt00127c

    Article  CAS  PubMed  Google Scholar 

  12. Levi, S., A. Luzzago, G. Cesareni, A. Cozzi, F. Franceschinelli, A. Albertini and P. Arosio (1988) Mechanism of ferritin iron uptake: activity of the H-chain and deletion mapping of the ferro-oxidase site. A study of iron uptake and ferro-oxidase activity of human liver, recombinant H-chain ferritins, and of two H-chain deletion mutants. J Biol Chem 263(34): 18086–18092

  13. Muhammad JS, Bajbouj K, Shafarin J, Hamad M (2020) Estrogen-induced epigenetic silencing of FTH1 and TFRC genes reduces liver cancer cell growth and survival. Epigenetics 15(12):1302–1318. https://doi.org/10.1080/15592294.2020.1770917

    Article  PubMed  PubMed Central  Google Scholar 

  14. Alkhateeb AA, Connor JR (2013) The significance of ferritin in cancer: anti-oxidation, inflammation and tumorigenesis. Biochim Biophys Acta 1836(2):245–254. https://doi.org/10.1016/j.bbcan.2013.07.002

    Article  CAS  PubMed  Google Scholar 

  15. Alkhateeb AA, Han B, Connor JR (2013) Ferritin stimulates breast cancer cells through an iron-independent mechanism and is localized within tumor-associated macrophages. Breast Cancer Res Treat 137(3):733–744. https://doi.org/10.1007/s10549-012-2405-x

    Article  CAS  PubMed  Google Scholar 

  16. Buranrat B, Connor JR (2015) Cytoprotective effects of ferritin on doxorubicin-induced breast cancer cell death. Oncol Rep 34(5):2790–2796. https://doi.org/10.3892/or.2015.4250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Vaughn CB, Weinstein R, Bond B, Rice R, Vaughn RW, McKendrick A, Ayad G, Rockwell MA, Rocchio R (1987) Ferritin content in human cancerous and noncancerous colonic tissue. Cancer Invest 5(1):7–10. https://doi.org/10.3109/07357908709020300

    Article  CAS  PubMed  Google Scholar 

  18. van Niel G, D’Angelo G, Raposo G (2018) Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol 19(4):213–228. https://doi.org/10.1038/nrm.2017.125

    Article  CAS  PubMed  Google Scholar 

  19. An T, Qin S, Xu Y, Tang Y, Huang Y, Situ B, Inal JM, Zheng L (2015) Exosomes serve as tumour markers for personalized diagnostics owing to their important role in cancer metastasis. J Extracell Vesicles 4:27522. https://doi.org/10.3402/jev.v4.27522

    Article  PubMed  Google Scholar 

  20. Milane L, Singh A, Mattheolabakis G, Suresh M, Amiji MM (2015) Exosome mediated communication within the tumor microenvironment. J Control Release 219:278–294. https://doi.org/10.1016/j.jconrel.2015.06.029

    Article  CAS  PubMed  Google Scholar 

  21. Mostafazadeh M, Kahroba H, Haiaty S, TazeKand AP, Samadi N, Rahbarghazi R, Nouri M (2022) In vitro exosomal transfer of Nrf2 led to the oxaliplatin resistance in human colorectal cancer LS174T cells. Cell Biochem Funct 40(4):391–402. https://doi.org/10.1002/cbf.3703

    Article  CAS  PubMed  Google Scholar 

  22. Arneth, B. (2019) Tumor microenvironment. Medicina (Kaunas) 56(1). https://doi.org/10.3390/medicina56010015

  23. Jung M, Mertens C, Brune B (2015) Macrophage iron homeostasis and polarization in the context of cancer. Immunobiology 220(2):295–304. https://doi.org/10.1016/j.imbio.2014.09.011

    Article  CAS  PubMed  Google Scholar 

  24. Badawi MA, Abouelfadl DM, El-Sharkawy SL, El-Aal WE, Abbas NF (2015) Tumor-associated macrophage (TAM) and angiogenesis in human colon carcinoma. Open Access Maced J Med Sci 3(2):209–214. https://doi.org/10.3889/oamjms.2015.044

    Article  PubMed  PubMed Central  Google Scholar 

  25. Lan J, Sun L, Xu F, Liu L, Hu F, Song D, Hou Z, Wu W, Luo X, Wang J, Yuan X, Hu J, Wang G (2019) M2 macrophage-derived exosomes promote cell migration and invasion in colon cancer. Cancer Res 79(1):146–158. https://doi.org/10.1158/0008-5472.CAN-18-0014

    Article  CAS  PubMed  Google Scholar 

  26. Ma YS, Wu TM, Ling CC, Yu F, Zhang J, Cao PS, Gu LP, Wang HM, Xu H, Li L, Wu ZJ, Wang GR, Li W, Lin QL, Liu JB, Fu D (2021) M2 macrophage-derived exosomal microRNA-155-5p promotes the immune escape of colon cancer by downregulating ZC3H12B. Mol Ther Oncolytics 20:484–498. https://doi.org/10.1016/j.omto.2021.02.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Pinto ML, Rios E, Duraes C, Ribeiro R, Machado JC, Mantovani A, Barbosa MA, Carneiro F, Oliveira MJ (2019) The two faces of tumor-associated macrophages and their clinical significance in colorectal cancer. Front Immunol 10:1875. https://doi.org/10.3389/fimmu.2019.01875

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Tang Z, Kang B, Li C, Chen T, Zhang Z (2019) GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res 47(W1):W556-w560. https://doi.org/10.1093/nar/gkz430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Chanput W, Mes JJ, Wichers HJ (2014) THP-1 cell line: an in vitro cell model for immune modulation approach. Int Immunopharmacol 23(1):37–45. https://doi.org/10.1016/j.intimp.2014.08.002

    Article  CAS  PubMed  Google Scholar 

  30. Locati M, Curtale G, Mantovani A (2020) Diversity, mechanisms, and significance of macrophage plasticity. Annu Rev Pathol 15:123–147. https://doi.org/10.1146/annurev-pathmechdis-012418-012718

    Article  CAS  PubMed  Google Scholar 

  31. Genin M, Clement F, Fattaccioli A, Raes M, Michiels C (2015) M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide. BMC Cancer 15:577. https://doi.org/10.1186/s12885-015-1546-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Xu J, Wan Z, Zhou B (2019) Drosophila ZIP13 is posttranslationally regulated by iron-mediated stabilization. Biochim Biophys Acta Mol Cell Res 1866(9):1487–1497. https://doi.org/10.1016/j.bbamcr.2019.06.009

    Article  CAS  PubMed  Google Scholar 

  33. Catalano M, O’Driscoll L (2020) Inhibiting extracellular vesicles formation and release: a review of EV inhibitors. J Extracell Vesicles 9(1):1703244. https://doi.org/10.1080/20013078.2019.1703244

    Article  CAS  PubMed  Google Scholar 

  34. Wang H, An P, Xie E, Wu Q, Fang X, Gao H, Zhang Z, Li Y, Wang X, Zhang J, Li G, Yang L, Liu W, Min J, Wang F (2017) Characterization of ferroptosis in murine models of hemochromatosis. Hepatology 66(2):449–465. https://doi.org/10.1002/hep.29117

    Article  CAS  PubMed  Google Scholar 

  35. Wan Z, Xu J, Huang Y, Zhai Y, Ma Z, Zhou B, Cao Z (2020) Elevating bioavailable iron levels in mitochondria suppresses the defective phenotypes caused by PINK1 loss-of-function in Drosophila melanogaster. Biochem Biophys Res Commun 532(2):285–291. https://doi.org/10.1016/j.bbrc.2020.08.002

    Article  CAS  PubMed  Google Scholar 

  36. Xu J, Liu S, Cui Z, Wang X, Ning T, Wang T, Zhang N, Xie S, Min L, Zhang S, Liang C, Zhu S (2021) Ferrostatin-1 alleviated TNBS induced colitis via the inhibition of ferroptosis. Biochem Biophys Res Commun 573:48–54. https://doi.org/10.1016/j.bbrc.2021.08.018

    Article  CAS  PubMed  Google Scholar 

  37. Jung M, Mertens C, Tomat E, Brune B (2019) Iron as a central player and promising target in cancer progression. Int J Mol Sci 20(2). https://doi.org/10.3390/ijms20020273

  38. Thevenod F (2018) Iron and its role in cancer defense: a double-edged sword. Met Ions Life Sci 18. https://doi.org/10.1515/9783110470734-021

  39. Hou W, Xie Y, Song X, Sun X, Lotze MT, Zeh HJ 3rd, Kang R, Tang D (2016) Autophagy promotes ferroptosis by degradation of ferritin. Autophagy 12(8):1425–1428. https://doi.org/10.1080/15548627.2016.1187366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kakhlon O, Gruenbaum Y, Cabantchik ZI (2002) Ferritin expression modulates cell cycle dynamics and cell responsiveness to H-ras-induced growth via expansion of the labile iron pool. Biochem J 363(Pt 3):431–436. https://doi.org/10.1042/0264-6021:3630431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Hu W, Zhou C, Jing Q, Li Y, Yang J, Yang C, Wang L, Hu J, Li H, Wang H, Yuan C, Zhou Y, Ren X, Tong X, Du J, Wang Y (2021) FTH promotes the proliferation and renders the HCC cells specifically resist to ferroptosis by maintaining iron homeostasis. Cancer Cell Int 21(1):709. https://doi.org/10.1186/s12935-021-02420-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Li JY, Paragas N, Ned RM, Qiu A, Viltard M, Leete T, Drexler IR, Chen X, Sanna-Cherchi S, Mohammed F, Williams D, Lin CS, Schmidt-Ott KM, Andrews NC, Barasch J (2009) Scara5 is a ferritin receptor mediating non-transferrin iron delivery. Dev Cell 16(1):35–46. https://doi.org/10.1016/j.devcel.2008.12.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Zhao M, Zhou B (2020) A distinctive sequence motif in the fourth transmembrane domain confers ZIP13 iron function in Drosophila melanogaster. Biochim Biophys Acta Mol Cell Res 1867(2):118607. https://doi.org/10.1016/j.bbamcr.2019.118607

    Article  CAS  PubMed  Google Scholar 

  44. Min L, Zhu S, Chen L, Liu X, Wei R, Zhao L, Yang Y, Zhang Z, Kong G, Li P, Zhang S (2019) Evaluation of circulating small extracellular vesicles derived miRNAs as biomarkers of early colon cancer: a comparison with plasma total miRNAs. J Extracell Vesicles 8(1):1643670. https://doi.org/10.1080/20013078.2019.1643670

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Guo J, Wang X, Guo Q, Zhu S, Li P, Zhang S, Min L (2022) M2 Macrophage derived extracellular vesicle-mediated transfer of MiR-186-5p promotes colon cancer progression by targeting DLC1. Int J Biol Sci 18(4):1663–1676. https://doi.org/10.7150/ijbs.69405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Wang W, Knovich MA, Coffman LG, Torti FM, Torti SV (2010) Serum ferritin: past, present and future. Biochim Biophys Acta 1800(8):760–769. https://doi.org/10.1016/j.bbagen.2010.03.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Ramirez-Carmona, W., B. Diaz-Fabregat, A. Yuri Yoshigae, A. Musa de Aquino, W. R. Scarano, A. C. de Souza Castilho, J. Avansini Marsicano, R. Leal do Prado, J. P. Pessan and L. de Oliveira Mendes (2021) Are serum ferritin levels a reliable cancer biomarker? A systematic review and meta-analysis. Nutr Cancer 1–10https://doi.org/10.1080/01635581.2021.1982996

  48. Feng Z, Chen JW, Feng JH, Shen F, Cai WS, Cao J, Xu B (2015) The association between serum ferritin with colorectal cancer. Int J Clin Exp Med 8(12):22293–22299

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Tappin JA, George WD, Bellingham AJ (1979) Effect of surgery on serum ferritin concentration in patients with breast cancer. Br J Cancer 40(4):658–660. https://doi.org/10.1038/bjc.1979.232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Figures 3a and 6 in this article were created by biorender.com (https://biorender.com/).

Funding

This work was supported by the Digestive Medical Coordinated Development Center of Beijing Hospitals Authority (XXZ015 to Jing Wu), the Special Scientific Research Fund for Tutor (YYDSZX201901 to Jing Wu), the Beijing Science and Technology Program (Z211100002921028 to Jing Wu), the Capital’s Funds for Health Improvement and Research (CFH2022-2–2025 to Jing Wu), and the Natural Science Foundation of Capital Medical University (PYZ21048 to Junxuan Xu).

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, China

    Zilu Cui, Wenkun Li, Mengran Zhao, Kuiliang Liu, Yi Yang, Nan Zhang, Li Min, Peng Li, Shutian Zhang, Junxuan Xu & Jing Wu

  2. Department of Gastroenterology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China

    Yadan Wang & Shuo Teng

Authors
  1. Zilu Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wenkun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yadan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mengran Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kuiliang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yi Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shuo Teng
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Li Min
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Peng Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Shutian Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Junxuan Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Jing Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Zilu Cui designed and performed the experiments, analyzed data, and wrote the original manuscript. Wenkun Li, Yadan Wang, Kuiliang Liu, Yi Yang, Shuo Teng, and Nan Zhang helped with some of the experiments and analyzed data. Mengran Zhao helped with manuscript editing and provided key advice. Li Min, Peng Li, and Shutian Zhang provided key reagents and advice. Junxuan Xu conceived and supervised the study, analyzed data, and wrote and edited the original manuscript. Jing Wu conceived and supervised the study, analyzed data, and reviewed and edited the manuscript.

Corresponding authors

Correspondence to Junxuan Xu or Jing Wu.

Ethics declarations

Ethics Approval and Consent to Participate

All patients enrolled in this study have signed the informed consents and this study was approved by the Ethics Committee of the Beijing Shijitan Hospital, Capital Medical University (Approval number: 2020–11).

Competing Interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

12011_2022_3488_MOESM1_ESM.doc

Supplementary file1 Figure S1. The protein levels of FTH1 in colon cancer cells and macrophages. a Western Blot assay was used to detect the protein levels of FTH1 in Caco-2, SW480, M1, and M2 macrophages. (DOC 66 KB)

12011_2022_3488_MOESM2_ESM.doc

Supplementary file2 Figure S2. The overexpression of FTH1 does not promote the cell migration ability of colon cancer cells. a The cell migration was assessed by wound healing assay in Caco-2 and SW480 cells transfected with FTH1 overexpression plasmids or empty vectors. b Quantitative results of wound healing assay. All data were presented as the mean ± SEM of 3 independent assays. *p < 0.05, **p < 0.01, ***p < 0.001. ****p < 0.0001 vs Vector group. (DOC 824 KB)

12011_2022_3488_MOESM3_ESM.doc

Supplementary file3 Figure S3. M2 macrophage-derived exosomes promote colon cancer cell proliferation, but the effect was significantly attenuated by GW4869 (inhibitors of exosome). a After co-culture with supernatant medium from macrophage, EdU assay was used to detect the proliferation ability of Caco-2 and SW480 cells. b Quantitative results of EdU assay. All data were presented as the mean ± SEM of 3 independent assays. *p < 0.05, **p < 0.01, ***p < 0.001. ****p < 0.0001 vs Vector group. (DOC 972 KB)

Supplementary file4 Table S1. Primary antibodies used in this study. (DOCX 15 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cui, Z., Li, W., Wang, Y. et al. M2 Macrophage-Derived Exosomal Ferritin Heavy Chain Promotes Colon Cancer Cell Proliferation. Biol Trace Elem Res 201, 3717–3728 (2023). https://doi.org/10.1007/s12011-022-03488-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-022-03488-w

Keywords

Search

Navigation