Skip to main content
SpringerLink
Log in

Differences in chemotaxis of human mesenchymal stem cells and cervical cancer cells

  • Published:
Apoptosis Aims and scope Submit manuscript

Abstract

In the last decade, there has been a rapid expansion in tumor targeted therapy using mesenchymal stem cells (MSCs) based on their unique tropism towards cancer cells. Despite similarities in morphology, immunophenotype, and differential potent in vitro, MSCs originated from different tissues do not necessarily have equivalent biological behaviors. It is important to screen the most chemotactic MSCs to cancer cells. In this study, different MSCs were isolated from various human tissues including adipose, umbilical cord, amniotic membrane, and chorion. The chemotaxis of human MSCs to cervical cancer cells was measured by CCK-8, ELISA and Transwell invasion assays. Western blotting was performed to explore the underlying mechanisms. MSCs derived from distinct sources can be differently recruited to cervical cancer cells, among which chorion-derived MSC (CD-MSC) possessed the strongest tropic capacity. CXCL12 was found to be highly secreted by cervical cancer cells, in parallel with the expression of CXCR4 in all MSCs. CD-MSC displayed the highest level of CXCR4. These results indicated that CXCL12/CXCR4 pathway contributed to the different chemotaxis to cervical cancer cells of each MSCs. This study proposed that CD-MSC with the highest CXCR4 expression is a promising therapeutic vehicle for targeted therapy in cervical 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
Fig. 7

Similar content being viewed by others

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

AMD-MSC:

Amniotic membrane-derived MSC

ANOVA:

Analysis of variance

ATCC:

American Type Culture Collection

ATD-MSC:

Adipose tissue-derived MSC

BCA:

bicinchoninic acid

BMD-MSC:

Bone marrow-derived MSC

BSA:

Bovine serum album

BSS:

Balanced salt solution

Calcein-AM:

Calcein acetoxymethyl ester

CCK-8:

Cell Counting Kit-8

CD-MSC:

Chorion-derived MSC

CM:

Conditioned medium

DMEM:

Dulbecco’s Modified Eagle Medium

ECL:

Efficient chemiluminescence

FBS:

Fetal bovine serum

FITC:

Fluorescein isothiocyanate

HPV:

Human papillomavirus

ISCT:

The International Society for Cellular Therapy

MSC:

Mesenchymal stem cell

Pen-Strep:

Penicillin–streptomycin

PE:

Phycoerythrin

PI:

Propidium iodide

PVDF:

Polyvinylidene fluoride

RIPA:

Radio-immunoprecipitation assay

SD:

Standard deviation

SDS-PAGE:

Sodium dodecyl sulfate–polyacrylamide gel electrophoresis

UCD-MSC:

Umbilical cord-derived MSC

References

  1. Sung H, Ferlay J, Siegel RL et al (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209–249

    Article  PubMed  Google Scholar 

  2. Zhao F, Qiao Y (2019) Cervical cancer prevention in China: a key to cancer control. Lancet 393:969–970

    Article  PubMed  Google Scholar 

  3. Bao H, Zhang L, Wang L et al (2018) Significant variations in the cervical cancer screening rate in China by individual-level and geographical measures of socioeconomic status: a multilevel model analysis of a nationally representative survey dataset. Cancer Med 7:2089–2100

    Article  PubMed  PubMed Central  Google Scholar 

  4. Arbyn M, Weiderpass E, Bruni L et al (2020) Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. Lancet Glob Health 8:e191–e203

    Article  PubMed  Google Scholar 

  5. Wei M, Zhou W, Bi Y, Wang H, Liu Y, Zhang ZJ (2019) Rising mortality rate of cervical cancer in younger women in urban China. J Gen Intern Med 34:281–284

    Article  PubMed  Google Scholar 

  6. Koh WJ, Abu-Rustum NR, Bean S et al (2019) Cervical cancer, version 3.2019, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 17:64–84

    Article  CAS  PubMed  Google Scholar 

  7. Griffiths MJ, Winship AL, Hutt KJ (2020) Do cancer therapies damage the uterus and compromise fertility? Hum Reprod Update 26:161–173

    Article  CAS  PubMed  Google Scholar 

  8. Spears N, Lopes F, Stefansdottir A et al (2019) Ovarian damage from chemotherapy and current approaches to its protection. Hum Reprod Update 25:673–693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Griffin MD, Ritter T, Mahon BP (2010) Immunological aspects of allogeneic mesenchymal stem cell therapies. Hum Gene Ther 21:1641–1655

    Article  CAS  PubMed  Google Scholar 

  10. Pittenger MF, Mackay AM, Beck SC et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    Article  CAS  PubMed  Google Scholar 

  11. Uccelli A, Moretta L, Pistoia V (2008) Mesenchymal stem cells in health and disease. Nat Rev Immunol 8:726–736

    Article  CAS  PubMed  Google Scholar 

  12. Hu YL, Fu YH, Tabata Y, Gao JQ (2010) Mesenchymal stem cells: a promising targeted-delivery vehicle in cancer gene therapy. J Control Release 147:154–162

    Article  CAS  PubMed  Google Scholar 

  13. Chulpanova DS, Kitaeva KV, Tazetdinova LG, James V, Rizvanov AA, Solovyeva VV (2018) Application of mesenchymal stem cells for therapeutic agent delivery in anti-tumor treatment. Front Pharmacol 9:259

    Article  PubMed  PubMed Central  Google Scholar 

  14. Kemp KC, Hows J, Donaldson C (2005) Bone marrow-derived mesenchymal stem cells. Leuk Lymphoma 46:1531–1544

    Article  PubMed  Google Scholar 

  15. Rodriguez AM, Elabd C, Amri EZ, Ailhaud G, Dani C (2005) The human adipose tissue is a source of multipotent stem cells. Biochimie 87:125–128

    Article  CAS  PubMed  Google Scholar 

  16. Ding DC, Chang YH, Shyu WC, Lin SZ (2015) Human umbilical cord mesenchymal stem cells: a new era for stem cell therapy. Cell Transplant 24:339–347

    Article  PubMed  Google Scholar 

  17. Papait A, Vertua E, Magatti M, et al (2020) Mesenchymal stromal cells from fetal and maternal placenta possess key similarities and differences: potential implications for their applications in regenerative medicine. Cells 9.

  18. Camernik K, Mihelic A, Mihalic R et al (2019) Skeletal-muscle-derived mesenchymal stem/stromal cells from patients with osteoarthritis show superior biological properties compared to bone-derived cells. Stem Cell Res 38:101465

    Article  CAS  PubMed  Google Scholar 

  19. Reinisch A, Etchart N, Thomas D et al (2015) Epigenetic and in vivo comparison of diverse MSC sources reveals an endochondral signature for human hematopoietic niche formation. Blood 125:249–260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wu M, Zhang R, Zou Q et al (2018) Comparison of the biological characteristics of mesenchymal stem cells derived from the human placenta and umbilical cord. Sci Rep 8:5014

    Article  PubMed  PubMed Central  Google Scholar 

  21. Horwitz EM, Le Blanc K, Dominici M et al (2005) Clarification of the nomenclature for MSC: the International society for cellular therapy position statement. Cytotherapy 7:393–395

    Article  CAS  PubMed  Google Scholar 

  22. Dominici M, Le Blanc K, Mueller I et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. the International Society for Cellular Therapy position statement. Cytotherapy 8:315–317

    Article  CAS  PubMed  Google Scholar 

  23. Calloni R, Cordero EA, Henriques JA, Bonatto D (2013) Reviewing and updating the major molecular markers for stem cells. Stem Cells Dev 22:1455–1476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Mildmay-White A, Khan W (2017) Cell surface markers on adipose-derived stem cells: a systematic review. Curr Stem Cell Res Ther 12:484–492

    Article  CAS  PubMed  Google Scholar 

  25. Baer PC, Kuci S, Krause M et al (2013) Comprehensive phenotypic characterization of human adipose-derived stromal/stem cells and their subsets by a high throughput technology. Stem Cells Dev 22:330–339

    Article  CAS  PubMed  Google Scholar 

  26. Li W, Song Y, Pan C, Yu J, Zhang J, Zhu X. (2021) Aquaporin-8 is a novel marker for progression of human cervical cancer cells. Cancer Biomark.

  27. Brown C, McKee C, Bakshi S et al (2019) Mesenchymal stem cells: cell therapy and regeneration potential. J Tissue Eng Regen Med 13:1738–1755

    Article  CAS  PubMed  Google Scholar 

  28. Li L, Guan Y, Liu H et al (2011) Silica nanorattle-doxorubicin-anchored mesenchymal stem cells for tumor-tropic therapy. ACS Nano 5:7462–7470

    Article  CAS  PubMed  Google Scholar 

  29. Deng W, Bivalacqua TJ, Chattergoon NN, Jeter JR Jr, Kadowitz PJ (2004) Engineering ex vivo-expanded marrow stromal cells to secrete calcitonin gene-related peptide using adenoviral vector. Stem Cells 22:1279–1291

    Article  CAS  PubMed  Google Scholar 

  30. Kern S, Eichler H, Stoeve J, Kluter H, Bieback K (2006) Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 24:1294–1301

    Article  CAS  PubMed  Google Scholar 

  31. Mueller SM, Glowacki J (2001) Age-related decline in the osteogenic potential of human bone marrow cells cultured in three-dimensional collagen sponges. J Cell Biochem 82:583–590

    Article  CAS  PubMed  Google Scholar 

  32. Stenderup K, Justesen J, Clausen C, Kassem M (2003) Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone 33:919–926

    Article  PubMed  Google Scholar 

  33. Wagner W, Ho AD, Zenke M (2010) Different facets of aging in human mesenchymal stem cells. Tissue Eng Part B 16:445–453

    Article  Google Scholar 

  34. Yang YK, Ogando CR, Wang See C, Chang TY, Barabino GA (2018) Changes in phenotype and differentiation potential of human mesenchymal stem cells aging in vitro. Stem Cell Res Ther 9:131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Siennicka K, Zolocinska A, Debski T, Pojda Z (2021) Comparison of the donor age-dependent and in vitro culture-dependent mesenchymal stem cell aging in rat model. Stem Cells Int 2021:6665358

    Article  PubMed  PubMed Central  Google Scholar 

  36. Fafian-Labora JA, Morente-Lopez M, Arufe MC (2019) Effect of aging on behaviour of mesenchymal stem cells. World J Stem Cells 11:337–346

    Article  PubMed  PubMed Central  Google Scholar 

  37. Ridge SM, Sullivan FJ, Glynn SA (2017) Mesenchymal stem cells: key players in cancer progression. Mol Cancer 16:31

    Article  PubMed  PubMed Central  Google Scholar 

  38. Li P, Gong Z, Shultz LD, Ren G (2019) Mesenchymal stem cells: From regeneration to cancer. Pharmacol Ther 200:42–54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kucerova L, Matuskova M, Hlubinova K, Altanerova V, Altaner C (2010) Tumor cell behaviour modulation by mesenchymal stromal cells. Mol Cancer 9:129

    Article  PubMed  PubMed Central  Google Scholar 

  40. Garcia-Rocha R, Moreno-Lafont M, Mora-Garcia ML et al (2015) Mesenchymal stromal cells derived from cervical cancer tumors induce TGF-beta1 expression and IL-10 expression and secretion in the cervical cancer cells, resulting in protection from cytotoxic T cell activity. Cytokine 76:382–390

    Article  CAS  PubMed  Google Scholar 

  41. de Lourdes M-G, Garcia-Rocha R, Morales-Ramirez O et al (2016) Mesenchymal stromal cells derived from cervical cancer produce high amounts of adenosine to suppress cytotoxic T lymphocyte functions. J Transl Med 14:302

    Article  Google Scholar 

  42. Montesinos JJ, Mora-Garcia Mde L, Mayani H et al (2013) In vitro evidence of the presence of mesenchymal stromal cells in cervical cancer and their role in protecting cancer cells from cytotoxic T cell activity. Stem Cells Dev 22:2508–2519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Yi T, Song SU (2012) Immunomodulatory properties of mesenchymal stem cells and their therapeutic applications. Arch Pharm Res 35:213–221

    Article  CAS  PubMed  Google Scholar 

  44. Galipeau J (2013) The mesenchymal stromal cells dilemma–does a negative phase III trial of random donor mesenchymal stromal cells in steroid-resistant graft-versus-host disease represent a death knell or a bump in the road? Cytotherapy 15:2–8

    Article  PubMed  Google Scholar 

  45. Fakiruddin KS, Ghazalli N, Lim MN, Zakaria Z, Abdullah S (2018) Mesenchymal stem cell expressing TRAIL as targeted therapy against sensitised tumour. Int J Mol Sci 19.

  46. Yadav SS, Prasad SB, Prasad CB et al (2016) CXCL12 is a key regulator in tumor microenvironment of cervical cancer: an in vitro study. Clin Exp Metastasis 33:431–439

    Article  CAS  PubMed  Google Scholar 

  47. Huang Y, Zhang J, Cui ZM, Zhao J, Zheng Y (2013) Expression of the CXCL12/CXCR4 and CXCL16/CXCR6 axes in cervical intraepithelial neoplasia and cervical cancer. Chin J Cancer 32:289–296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Zheng J, Li H, He L et al (2019) Preconditioning of umbilical cord-derived mesenchymal stem cells by rapamycin increases cell migration and ameliorates liver ischaemia/reperfusion injury in mice via the CXCR4/CXCL12 axis. Cell Prolif 52:e12546

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by grants from National Natural Science Foundation of China (NO. 81671809).

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, No. 109 Xueyuan Xi Road, Wenzhou, 325027, Zhejiang, China

    Yizuo Song, Ruyi Li, Miaomiao Ye, Chunyu Pan, Lihong Zheng, Zhi-wei Wang & Xueqiong Zhu

Authors
  1. Yizuo Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ruyi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Miaomiao Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chunyu Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lihong Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zhi-wei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xueqiong Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

XZ and ZW conceived and designed the study. YS and RL collected the tissues from patients and did the cell experiments. MY and CP also participated in tissue collection. LZ analyzed and interpreted the data. YS drafted the manuscript. XZ and ZW revised the manuscript. XZ supervised the study. All authors gave final approval of the manuscript submission and publication.

Corresponding authors

Correspondence to Zhi-wei Wang or Xueqiong Zhu.

Ethics declarations

Competing interest

The authors declare that they have no competing interests.

Ethical approval

This study was approved by the Ethical Committee of the Second Affiliated Hospital of Wenzhou Medical University (No. 2016kykt31).

Consent to participate

Samples were collected from patients who provided written informed consent, and all works were performed in accordance with the Declaration of Helsinki.

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.

Supplementary file1 (PDF 1075 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Song, Y., Li, R., Ye, M. et al. Differences in chemotaxis of human mesenchymal stem cells and cervical cancer cells. Apoptosis 27, 840–851 (2022). https://doi.org/10.1007/s10495-022-01749-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10495-022-01749-6

Keywords

Search

Navigation