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Cartilage oligomeric matrix protein (COMP) promotes cell proliferation in early-onset colon cancer tumorigenesis

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Abstract

Background

Colon cancer (CC) is the third most commonly diagnosed cancer in the USA. While the overall incidence is declining, it is rising alarmingly in young patients (EOCC). CC in young patients tends to be more aggressive and often diagnosed at more advanced stages and portend poorer prognosis. Our recently published data showed that EOCC is a distinct disease with unique molecular features compared to late-onset CC (LOCC). The Cartilage Oligomeric Matrix Protein (COMP) was shown to be significantly upregulated in EOCC and correlated with poor survival. However, the role of COMP in CC tumorigenesis, especially in young patients, is not well understood. Thus, the aim of this study was to elucidate the role of COMP in CC tumorigenesis by modulating COMP levels in vitro and test how it affects proliferation. Then, patient samples were evaluated by testing the levels of proliferation marker Ki67. In addition, this study investigates whether higher transcriptional mRNA levels of COMP seen in more aggressive early-onset CC correlate with protein levels compared to late-onset CC.

Methods

COMP mRNA levels in fresh frozen colon tumors (young: n = 5; old: n = 5) were assessed by quantitative PCR (qPCR). Additionally, CC cell lines were profiled for COMP expression to choose an in vitro model to study the role of COMP in CC tumorigenesis. HT-29 (low COMP expression) and CaCo-2 (high COMP expression) cells were used for in vitro proliferation studies. Immunohistochemical (IHC) analysis was conducted to assess COMP and Ki67 protein levels in formalin-fixed paraffin-embedded (FFPE) colon tumors.

Results

Significantly higher COMP expression levels were observed in fresh frozen EOCC compared to LOCC tumors. This observation confirmed our previously reported results from NanoString gene expression assay using FFPE samples. Cell proliferation was significantly increased in HT-29 and CaCo-2 cells upon treatment with human recombinant COMP protein after 48 and 72 h (P < 0.05). This increase was more profound in HT-29 cells. Staining for COMP and Ki67 revealed high COMP protein levels in EOCC compared to LOCC patients.

Conclusion

COMP mRNA and protein levels are significantly higher in EOCC patients. Higher COMP levels correlate with increased proliferation suggesting a role in CC tumorigenesis.

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Acknowledgements

We would like to thank the patients without whom this work would not have been possible.

Funding

This work was supported by the SAGES research grant awarded to VNN.

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Authors and Affiliations

  1. Department of Surgery, University of Arizona, Tucson, AZ, 85724, USA

    V. N. Nfonsam, H. C. Jecius, P. N. Omesiete & J. Jandova

  2. Department of Medicine, University of Arizona, Tucson, AZ, 85724, USA

    J. Janda

  3. Division of Hematology and Oncology, Department of Medicine, Banner-University of Arizona Cancer Center, Tucson, AZ, 85724, USA

    E. Elquza & A. J. Scott

  4. Children’s Hospital of Eastern Ontario, Ottawa, ON, K1H8L1, Canada

    L. E. Nfonsam

Authors
  1. V. N. Nfonsam
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  2. H. C. Jecius
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  3. J. Janda
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  4. P. N. Omesiete
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  5. E. Elquza
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  6. A. J. Scott
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  7. L. E. Nfonsam
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  8. J. Jandova
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Contributions

VNN—conception and design; PNO, HCJ—data acquisition; JJ—IHC data acquisition; LEN, EE, AJS—manuscript review; JJ—design, conception, manuscript preparation, data interpretation, data analysis.

Corresponding author

Correspondence to V. N. Nfonsam.

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Disclosures

V.N. Nfonsam, H.C. Jecius, J. Janda, P. N. Omesiete, E. Elquza, A.J. Scott, L. E. Nfonsam, and J. Jandova, declare no conflict of interest or financial ties to disclose.

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Nfonsam, V.N., Jecius, H.C., Janda, J. et al. Cartilage oligomeric matrix protein (COMP) promotes cell proliferation in early-onset colon cancer tumorigenesis. Surg Endosc 34, 3992–3998 (2020). https://doi.org/10.1007/s00464-019-07185-z

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  • DOI: https://doi.org/10.1007/s00464-019-07185-z

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