Skip to main content

Advertisement

SpringerLink
Log in

Comparing Migratory and Mechanical Properties of Human Bone Marrow-Derived Mesenchymal Stem Cells with Colon Cancer Cells In Vitro

  • Original Research
  • Published:
Journal of Gastrointestinal Cancer Aims and scope Submit manuscript

Abstract

Background

Colon cancer cells can migrate and metastasize by undergoing epithelial-to-mesenchymal transition (EMT). Mesenchymal stem cells (MSCs) are non-cancerous, multipotent adult stem cells, which can also migrate. In this study, we wanted to compare the biological, physical, and functional properties of these migratory cells.

Materials and methods

HT-29 and HCT-116, two human colon carcinoma cell lines, represent less aggressive and more aggressive cancer cells, respectively. MSCs were isolated from human bone marrow. After confirming the identity of all the cell types, they were evaluated for E-cadherin, β1-integrin, Vimentin, ZEB-1, β-catenin, and 18S rRNA using Q-PCR. MMP-2 and MMP-9 activity were evaluated using gelatin zymography. Functional tests like wound healing assay, migration assay, and invasion assay were also done. Biomechanical properties like cell stiffness and non-specific adhesion (between indenter probe and cell membrane) were evaluated through nanoindentation using atomic force microscopy (AFM).

Results

Expression of EMT and stem cell markers showed typical expression patterns for HT-29, HCT-116, and MSCs. Functional tests showed that MSCs migrated faster than malignant cells. MMP-2 and MMP-9 activity reinforced this behavior. Interestingly, the migration/invasion capacity of MSCs was comparable to aggressive HCT-116, and more than HT-29. MSCs also showed the maximum cell stiffness and non-specific cell-probe adhesions, followed by HCT116 and HT29 cells.

Conclusions

Our findings indicate that the migratory properties of MSCs is comparable or even greater than that of cancer cells and despite their high migration potential, they also have the maximum stiffness.

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

Abbreviations

AFM:

Atomic force microscopy

BSE:

Bottom substrate effect

CRC:

Colorectal cancer

DMEM:

Dulbecco’s modified Eagle’s medium

E:

Elastic modulus

EMT:

Epithelial-to-mesenchymal transition

ECM:

Extracellular matrix

FBS:

Fetal bovine serum

MMP:

Matrix metalloproteinases

MSC:

Mesenchymal stem cells

MMuLV-RT:

Moloney murine leukemia virus-reverse transcriptase

PAF:

Peak value of adhesion force

PBS:

Phosphate-buffered saline

Q-PCR:

Quantitative PCR

STR:

Short tandem repeat

References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424. https://doi.org/10.3322/caac.21492.

    Article  Google Scholar 

  2. Son H, Moon A. Epithelial-mesenchymal transition and cell invasion. Toxicol Res. 2010;26:245–52. https://doi.org/10.5487/TR.2010.26.4.245.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Mochizuki M, Nakahara T. Establishment of xenogeneic serum-free culture methods for handling human dental pulp stem cells using clinically oriented in-vitro and in-vivo conditions. Stem Cell Res Ther. 2018;9:25. https://doi.org/10.1186/s13287-017-0761-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Luo D, Hu S, Tang C, Liu G. Mesenchymal stem cells promote cell invasion and migration and autophagy-induced epithelial-mesenchymal transition in A549 lung adenocarcinoma cells. Cell Biochem Funct. 2018;36:88–94. https://doi.org/10.1002/cbf.3320.

    Article  CAS  PubMed  Google Scholar 

  5. Friedl P, Alexander S. Cancer invasion and the microenvironment: plasticity and reciprocity. Cell. 2011;147:992–1009. https://doi.org/10.1016/j.cell.2011.11.016.

    Article  CAS  PubMed  Google Scholar 

  6. Zhou Z, Zheng C, Li S, Zhou X, Liu Z, He Q, et al. AFM nanoindentation detection of the elastic modulus of tongue squamous carcinoma cells with different metastatic potential. Nanomedicine. 2013;9:864–74. https://doi.org/10.1016/j.nano.2013.04.001.

    Article  CAS  PubMed  Google Scholar 

  7. Xu W, Mezencev R, Kim B, Wang L, Mcdonald JF, Sulcheck T. Cell stiffness is a biomarker of the metastatic potential of ovarian cancer cells. PLoS One. 2012;7:e46609. https://doi.org/10.1371/journal.pone.0046609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Managuli V, Roy S. Influencing factors in atomic force microscopy based mechanical characterization of biological cells. Exp Tech. 2017;41(6):673–87. https://doi.org/10.1007/s40799-017-0199-9.

    Article  Google Scholar 

  9. Managuli V, Roy S. Simultaneous analysis of elastic and nonspecific adhesive properties of thin sample and biological cell considering bottom substrate effect. J Biomech Eng. 2017;139(9):091008. https://doi.org/10.1115/1.4037289.

    Article  Google Scholar 

  10. Lee MH, Brass DA, Morris R, Composto RJ, Ducheyne P. The effect of non-specific interactions on cellular adhesion using model surfaces. Biomaterials. 2005;26:1721–30. https://doi.org/10.1016/j.biomaterials.2004.05.026.

    Article  CAS  PubMed  Google Scholar 

  11. Palmieri V, Lucchetti D, Maiorana A, Papi M, Maulucci G, Calapa F, et al. Mechanical and structural comparison between primary tumor and lymph node metastasis cells in colorectal cancer. Soft Matter. 2015;11:5719–26. https://doi.org/10.1039/c5sm01089f.

    Article  CAS  PubMed  Google Scholar 

  12. Pachenari M, Seyedpour SM, Janmaleki M, Shayan SB, Taranejoo S, Hosseinkhani H. Mechanical properties of cancer cytoskeleton depend on actin filaments to microtubules content: investigating different grades of colon cancer cell lines. J Biomech. 2014;47:373–9. https://doi.org/10.1016/j.jbiomech.2013.11.020.

    Article  CAS  PubMed  Google Scholar 

  13. Gurzu S, Silveanu C, Fetyko A, Butiurca V, Kovacs Z, Jung I. Systematic review of the old and new concepts in the epithelial-mesenchymal transition of colorectal cancer. World J Gastroenterol. 2016;22:6764–75. https://doi.org/10.3748/wjg.v22.i30.6764.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kunschmann T, Puder S, Fischer T, Steffen A, Rottner K, Mierka CT. The small GTPase Rac1 increases cell surface stiffness and enhances 3D migration into extracellular matrices. Sci Rep. 2019;9:7675. https://doi.org/10.1038/s41598-019-43975-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Reid SE, Zanivan S. Tumor stiffness extends its grip on the metastatic microenvironment. Mol Cell Oncol. 2017;4:e1372866. https://doi.org/10.1080/23723556.2017.1372866.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cross SE, Jin YS, Tondre J, Wong R, Rao JY, Gimzewski JK. AFM based analysis of human metastatic cancer cells. Nanotechnology. 2008;24:384003. https://doi.org/10.1088/0957-4484/19/38/384003.

    Article  CAS  Google Scholar 

  17. Steinestel K, Eder S, Schrader AJ, Steinestel J. Clinical significance of epithelial-mesenchymal transition. Clin Transl Med. 2014;3:17. https://doi.org/10.1186/2001-1326-3-17.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Ren F, Tang R, Zhang X, Madushi WM, Luo D, Dang Y, et al. Overexpression of MMP family members functions as prognostic biomarker for breast cancer patients: a systematic review and meta-analysis. PLoS One. 2015;10:e0135544. https://doi.org/10.1371/journal.pone.0135544.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Emons G, Spitzner M, Reineke S, Möller J, Auslander N, Kramer F, et al. Chemoradiotherapy resistance in colorectal cancer cells is mediated by Wnt/β-catenin signaling. Mol Cancer Res. 2017;15:1481–90. https://doi.org/10.1158/1541-7786.MCR-17-0205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This research did not receive any specific grant from funding agencies in public, commercial, or non-for-profit sectors.

Author information

Author notes

  1. Aditi Bhattacharya and Sumedha Saluja contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, 110029, India

    Aditi Bhattacharya, Sumedha Saluja, Sandeep Agrawal, Devanjan Dey & Sudip Sen

  2. Department of Applied Mechanics, Indian Institute of Technology, Delhi, New Delhi, 110016, India

    Vishwanath Managuli & Sitikantha Roy

  3. Department of Mechanical and Manufacturing Engineering, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India

    Vishwanath Managuli

  4. Department of Biochemistry, All India Institute of Medical Sciences, Raebareli, Uttar Pradesh, 229405, India

    Sandeep Agrawal

  5. Department of Orthopaedics, All India Institute of Medical Sciences, New Delhi, 110029, India

    Bhavuk Garg & Mohammed Tahir Ansari

Authors
  1. Aditi Bhattacharya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sumedha Saluja
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vishwanath Managuli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sandeep Agrawal
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Devanjan Dey
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bhavuk Garg
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mohammed Tahir Ansari
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sitikantha Roy
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Sudip Sen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sudip Sen.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

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

Scientific contribution of Aditi Bhattacharya and Sumedha Saluja are equal

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bhattacharya, A., Saluja, S., Managuli, V. et al. Comparing Migratory and Mechanical Properties of Human Bone Marrow-Derived Mesenchymal Stem Cells with Colon Cancer Cells In Vitro. J Gastrointest Canc 52, 882–891 (2021). https://doi.org/10.1007/s12029-020-00476-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12029-020-00476-y

Keywords

Search

Navigation