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Evaluation of CD44 and CD44v6 in Colorectal Carcinoma Patients: Soluble Forms in Relation to Tumor Tissue Expression and Metastasis

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Abstract

Introduction

It has been shown that CD44 may be associated with poor prognosis in various human malignancies. This study was designed to investigate and compare the prognostic relevance and clinical value of soluble forms of CD44 and its variant v6 (CD44v6) and their tissue expression in colorectal carcinoma.

Materials and methods

Serum levels of pre- and postoperative CD44 and CD44v6 molecules were evaluated in 37 colorectal cancer patients and compared to healthy individuals.

Results and discussion

The serum levels of soluble CD44 and CD44v6 showed no significant decrease after surgical resection of the tumor (p = 0.5). Both CD44 and CD44v6 serum levels either before or after surgery were significantly higher in patients than in normal individuals (p < 0.001). The serum level of CD44v6 molecule was higher in patients with lymph node metastasis than other patients (p = 0.05) implying the role of this molecule in tumor progression. Immunohistochemical staining showed expression of CD44 in 14.3% and CD44v6 in 42.9% of the tumor samples. The expression of CD44v6 was associated with metastatic involvement of lymph nodes (p = 0.03). CD44v6 expression was positively correlated with its level in the serum of patients (p = 0.04).

Conclusions

Results of this study showed that CD44v6 expression level either in the soluble form or in the cell membrane is associated with tumor metastasis indicating the importance of this molecule in progression of colorectal carcinoma. The serum levels of soluble CD44 as well as CD44v6 might be useful markers for tumor screening.

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References

  1. Hosseini SV, Izadpanah A, Yarmohammadi H. Epidemiological changes in colorectal cancer in Shiraz, Iran:1980–2000. ANZ J Surg. 2004;74:547–9.

    Article  PubMed  Google Scholar 

  2. Orr FW, Wang HH. Tumor cell interactions with the microvasculature: a rate-limiting step in metastasis. Surg Oncol Clin N Am. 2001;10:357–81.

    PubMed  CAS  Google Scholar 

  3. Iiizumi M, Mohinta S, Bandyopadhyay S, et al. Tumor–endothelial cell interactions: therapeutic potential. Microvasc Res. 2007;74:114–20.

    Article  PubMed  CAS  Google Scholar 

  4. Dalchau R, Kirkley J, Fabre JW. Monoclonal anti-body to a human leukocyte-specific membrane glyco-protein probably homologous to the leukocyte-common (L-C) antigen of the rat. Eur J Immunol. 1980;10:737–44.

    Article  PubMed  CAS  Google Scholar 

  5. Dianzani U, Malavasi F. Lymphocyte adhesion to endothelium. Crit Rev Immunol. 1995;15:167–200.

    PubMed  CAS  Google Scholar 

  6. Screaton GR, Bell MV, Jackson DG, et al. Genomic structure of DNA encoding the lymphocyte homing receptor CD44 reveals at least 12 alternatively spliced exons. Proc Natl Acad Sci USA. 1992;89:12160–4.

    Article  PubMed  CAS  Google Scholar 

  7. Günthert U, Hofmann M, Rudy W, et al. A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells. Cell. 1991;65:13–24.

    Article  PubMed  Google Scholar 

  8. Iida N, Bourguignon LYW. New CD44 splice variants associated with human breast cancers. J Cell Physiol. 1995;162:127–33.

    Article  PubMed  CAS  Google Scholar 

  9. Manten-Horst E, Danen EH, Smit L, et al. Expression of CD44 splice variants in human cutaneous melanoma and melanoma cell lines is related to tumor progression and metastatic potential. Int J Cancer Pred Oncol. 1995;64:182–8.

    Article  CAS  Google Scholar 

  10. Picker LJ, De Los Toyos J, Telen MJ, et al. Monoclonal antibodies against the CD44 [in(lu)-related p80] and pgp-1 antigens in man recognize the Hermes class of lymphocyte homing receptors. J Immunol. 1989;142:2046–51.

    PubMed  CAS  Google Scholar 

  11. Bazil V, Horejsi B. Shedding of the CD44 adhesion molecule from leukocytes induced by anti-CD44 monoclonal antibody simulating the effect of a natural receptor ligand. J Immunol. 1992;149:747–53.

    PubMed  CAS  Google Scholar 

  12. Ristamäki R, Joensuu H, Jalkanen S. Does soluble CD44 reflect the clinical behavior of human cancer? Curr Top Microbiol Immunol. 1996;213:155–66.

    PubMed  Google Scholar 

  13. Gansauge F, Gansauge S, Rau B, et al. Low serum levels of soluble CD44 variant 6 are significantly associated with poor prognosis in patients with pancreatic carcinoma. Cancer. 1997;80:1733–9.

    Article  PubMed  CAS  Google Scholar 

  14. Subramaniam V, Gardner H, Jothy S. Soluble CD44 secretion contributes to the acquisition of aggressive tumor phenotype in human colon cancer cells. Exp Molecular Pathol. 2007;83:341–6.

    Article  CAS  Google Scholar 

  15. Cichy J, Pure E. The liberation of CD44. J Cell Biol. 2003;161:839–43.

    Article  PubMed  CAS  Google Scholar 

  16. Andratschke M, Chaubal S, Pauli C, et al. Soluble CD44v6 is not a sensitive tumor marker in patients with head and neck squamous cell cancer. Anticancer Res. 2005;25:2821–6.

    PubMed  CAS  Google Scholar 

  17. Lein M, Jung K, Weiss S, et al. Soluble CD44 variants in the serum of patients with urological malignancies. Oncology. 1997;54:226–30.

    Article  PubMed  CAS  Google Scholar 

  18. Kainz C, Tempfer C, Winkler S, et al. Serum CD44 splice variants in cervical cancer patients. Cancer Lett. 1995;90:231–4.

    Article  PubMed  CAS  Google Scholar 

  19. Jung K, Lein M, Weiss S, et al. Soluble CD44 molecules in serum of patients with prostate cancer and benign prostatic hyperplasia. Eur J Cancer. 1996;32A:627–30.

    Article  PubMed  CAS  Google Scholar 

  20. Masson D, Denis MG, Denis M, et al. Soluble CD44: quantification and molecular repartition in plasma of patients with colorectal cancer. Br J Cancer. 1999;80:1995–2000.

    Article  PubMed  CAS  Google Scholar 

  21. Zalewski B. Levels of v5 and v6 CD44 splice variants in serum of patients with colorectal cancer are not correlated with pT stage, histopathological grade of malignancy and clinical features. World J Gastroenterol. 2004;10:583–5.

    PubMed  CAS  Google Scholar 

  22. Weg-Remers S, Hildebrandt U, Feifel G, et al. Soluble CD44 and CD44v6 serum levels in patients with colorectal cancer are independent of tumor stage and tissue expression of CD44v6. Am J Gastroenterol. 1998;93:790–4.

    Article  PubMed  CAS  Google Scholar 

  23. Yamane N, Tsujitani S, Makino M, et al. Soluble CD44 variant 6 as a prognostic indicator in patients with colorectal Cancer. Oncology. 1999;56:232–8.

    Article  PubMed  CAS  Google Scholar 

  24. Perez-Palma J, Marchena-Gomez J, Dorta-Espineira M, et al. Predictive factors of years of potential life lost by colorectal cancer. Eur J Gastroenterol Hepatol. 2008;20:766–72.

    Article  PubMed  Google Scholar 

  25. Mai SK, Welzel G, Hermann B, et al. Long-term outcome after combined radiochemotherapy for anal cancer—retrospective analysis of efficacy, prognostic factors, and toxicity. Onkologie. 2008;31:251–7.

    Article  PubMed  Google Scholar 

  26. Bendardaf R, Algars A, Elzagheid A, et al. Comparison of CD44 expression in primary tumours and metastases of colorectal cancer. Oncol Rep. 2006;16:741–6.

    PubMed  CAS  Google Scholar 

  27. Zhang JC, Wang ZR, Cheng YJ, et al. Expression of proliferating cell nuclear antigen and CD44 variant exon 6 in primary tumors and corresponding lymph node metastases of colorectal carcinoma with Dukes’ stage C or D. World J Gastroenterol. 2003;9:1482–6.

    PubMed  Google Scholar 

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Acknowledgement

The authors are grateful to Fatemeh Safaei, Saied Malekhosseini, and Hossein Golmoghaddam for providing invaluable assistance. This work was supported by grants 2287 and 2802 from Shiraz University of Medical Sciences.

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Authors and Affiliations

  1. Immunology Department, Medical School, Shiraz University of Medical Science, 71345-1798, Shiraz, Iran

    Zahra Amirghofran, Seyed Amir Jalali & Abbas Ghaderi

  2. Autoimmune Disease Research Center and Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Zahra Amirghofran

  3. Department of Surgery and Gastroentrohepatology Research Center, Nemazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran

    Seyed Vahid Hosseini & Behnam Sabayan

  4. Department of Pathology, Shiraz University of Medical Sciences, Shiraz, Iran

    Mohammad Vasei

  5. Cancer Research Institute, Shiraz University of Medical Sciences, Shiraz, Iran

    Abbas Ghaderi

Authors
  1. Zahra Amirghofran
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  2. Seyed Amir Jalali
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  3. Seyed Vahid Hosseini
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  4. Mohammad Vasei
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  5. Behnam Sabayan
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  6. Abbas Ghaderi
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Correspondence to Zahra Amirghofran.

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Amirghofran, Z., Jalali, S.A., Hosseini, S.V. et al. Evaluation of CD44 and CD44v6 in Colorectal Carcinoma Patients: Soluble Forms in Relation to Tumor Tissue Expression and Metastasis. J Gastrointest Canc 39, 73–78 (2008). https://doi.org/10.1007/s12029-009-9062-2

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  • DOI: https://doi.org/10.1007/s12029-009-9062-2

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