Increased soluble CD44 concentrations are associated with larger tumor size and lymph node metastasis in breast cancer patients

Sebastian Mayer, Axel Zur Hausen, Dirk Otto Watermann, Stefan Stamm, Markus Jäger, Gerald Gitsch, Elmar Stickeler

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Purpose: CD44 is a cell surface glycoprotein involved in cell-cell and cell-substrate interactions, which may be shed or released into circulation by proteolytic enzymatic mechanisms. Alternative splicing of CD44 and aberrant levels of soluble CD44 variants in the serum of cancer patients have been correlated to tumor progression and metastasis in different tumors including breast cancer. In this study we evaluated the clinical value of CD44 serum levels (sCD44) in patients with primary breast cancer. Methods: Concentrations of soluble isoforms sCD44std, sCD44v5 and sCD44v6 were determined with a sensitive ELISA and normalized against the total protein concentration (TP). Pre-operative serum samples from 82 patients and 67 age-matched healthy blood donors were analyzed. The results were correlated to clinico-pathological parameters (tumor size, grading, lymph node metastasis, etc.). Results: In sera of breast cancer patients, we detected elevated concentrations of sCD44v6 (P = 0.0001) and total protein TP (P = 0.0001) in comparison to healthy controls, whereas overall sCD44 (sCD44std) and sCD44v5 did not differ. Patients with sCD44v6-concentrations above the 75%-percentile showed an increased T stage (2.9 cm vs. 1.8 cm) as well as a higher risk for lymph node metastasis (55% vs. 35%). In breast cancer patients with lymph node metastasis the median value of sCD44v6 was significantly higher (P = 0.025) in comparison to patients without lymph node metastasis and healthy controls. Conclusions: Our data suggest an upregulated expression of alternatively spliced soluble CD44 isoforms in breast cancer patients. The specific alterations of certain CD44 isoform concentrations (especially sCD44v6) may reflect disturbances of the nuclear splicing machinery in tumor cells. The clinical significance of our findings are underlined by the positive correlation of elevated sCD44v6 concentrations and lymph node metastases (rs = 0.25).

Original languageEnglish
Pages (from-to)1229-1235
Number of pages7
JournalJournal of Cancer Research and Clinical Oncology
Issue number11
StatePublished - Nov 2008

Bibliographical note

Funding Information:
Acknowledgments This work was supported by a grant of the Deutsche Krebshilfe to E. S. (No. 107690)


  • Lymph node metastasis
  • Primary breast cancer
  • Soluble CD44
  • Tumor size

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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