Skip to main content

Advertisement

SpringerLink
Log in

Is mucin a determinant of peritoneal dissemination of gastrointestinal cancer? Analysis of mucin depletion in two preclinical models

  • Brief Research Article
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Background

Mucinous gastrointestinal cancers may indicate a higher propensity for widespread peritoneal seeding than their non-mucinous counterparts. We hypothesized that mucin content of gastrointestinal cancer cells and tumors is an indicator of cell viability and a determinant of the peritoneal tumor burden and tested our hypothesis in relevant experimental models.

Methods

MKN45 and LS174T models of human gastrointestinal cancer were treated with known mucin-depleting agents in vitro and in vivo, their mucin production was evaluated with Western blot immunohistochemistry, PAS staining and ELISA, and its correlation with cell viability and peritoneal tumor burden was analyzed.

Results

A relationship was found between the viability of cancer cells and their mucin levels in vitro. In agreement, when treated animal models were categorized into low- and high-burden groups (based on the weight and number of the peritoneal nodules), tumoral mucin levels were found to be significantly higher in the latter group.

Conclusions

Tumoral mucin is apparently among the factors that dictate the pattern and extent of the peritoneal spread of gastrointestinal cancer, where it allows for enhanced dissemination and redistribution. If further tested and validated, our hypothesis could lay the basis for the development of novel mucin-targeted strategies.

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

Similar content being viewed by others

References

  1. Sugarbaker PH. Peritoneum as the first-line of defense in carcinomatosis. J Surg Oncol. 2007;95:93–6.

    Article  PubMed  Google Scholar 

  2. Sugarbaker PH. Management of peritoneal-surface malignancy: the surgeon’s role. Langenbecks Arch Surg. 1999;384:576–87.

    Article  CAS  PubMed  Google Scholar 

  3. Esquivel J. Treatment of peritoneal surface malignancies. Surg Oncol Clin N Am. 2012;21:xv–xviii.

    Article  PubMed  Google Scholar 

  4. Mohamed F, Cecil T, Moran B, Sugarbaker P. A new standard of care for the management of peritoneal surface malignancy. Curr Oncol. 2011;18:e84–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Carmignani CP, Sugarbaker TA, Bromley CM, Sugarbaker PH. Intraperitoneal cancer dissemination: mechanisms of the patterns of spread. Cancer Metastasis Rev. 2003;22:465–72.

    Article  PubMed  Google Scholar 

  6. Hollingsworth MA, Swanson BJ. Mucins in cancer: protection and control of the cell surface. Nat Rev Cancer. 2004;4:45–60.

    Article  CAS  PubMed  Google Scholar 

  7. Jonckheere N, Skrypek N, Van Seuningen I. Mucins and tumor resistance to chemotherapeutic drugs. Biochim Biophys Acta. 2014;1846:142–51.

    CAS  PubMed  Google Scholar 

  8. Nath S, Mukherjee P. MUC1: a multifaceted oncoprotein with a key role in cancer progression. Trends Mol Med. 2014;20:332–42.

    Article  CAS  PubMed  Google Scholar 

  9. Singh A, Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene. 2010;29:4741–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Amini A, Masoumi-Moghaddam S, Ehteda A, Morris D. Bromelain and N-acetylcysteine inhibit proliferation and survival of gastrointestinal cancer cells in vitro: significance of combination therapy. J Exp Cli Cancer Res. 2014;33:92.

    Google Scholar 

  11. Amini A, Masoumi-Moghaddam S, Ehteda A, Liauw W, Morris DL. Depletion of mucin in mucin-producing human gastrointestinal carcinoma: results from in vitro and in vivo studies with bromelain and N-acetylcysteine. Oncotarget. 2015;6:33329–44.

    PubMed  PubMed Central  Google Scholar 

  12. Amini A, Masoumi-Moghaddam S and Morris DL. Utility of bromelain and N-acetylcysteine in treatment of peritoneal dissemination of gastrointestinal mucin-producing malignancies. Springer International Publishing; 2016.

  13. Gum JR Jr. Mucin genes and the proteins they encode: structure, diversity, and regulation. Am J Respir Cell Mol Biol. 1992;7:557–64.

    Article  CAS  PubMed  Google Scholar 

  14. Amini A, Masoumi-Moghaddam S and Morris DL, editors. Mucins and tumor biology. In: Utility of bromelain and N-acetylcysteine in treatment of peritoneal dissemination of gastrointestinal mucin-producing malignancies. Springer International Publishing; 2016. p. 43–57.

  15. Byrd JC, Bresalier RS. Mucins and mucin binding proteins in colorectal cancer. Cancer Metastasis Rev. 2004;23:77–99.

    Article  CAS  PubMed  Google Scholar 

  16. Sugarbaker PH. Pseudomyxoma peritonei. Cancer Treat Res. 1996;81:105–19.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, St George Hospital, The University of New South Wales, Gray Street, Kogarah, Sydney, NSW, 2217, Australia

    S. Masoumi-Moghaddam, A. Amini & D. L. Morris

Authors
  1. S. Masoumi-Moghaddam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Amini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. L. Morris
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Masoumi-Moghaddam.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Masoumi-Moghaddam, S., Amini, A. & Morris, D.L. Is mucin a determinant of peritoneal dissemination of gastrointestinal cancer? Analysis of mucin depletion in two preclinical models. Clin Transl Oncol 19, 261–264 (2017). https://doi.org/10.1007/s12094-016-1519-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-016-1519-8

Keywords

Search

Navigation