TY - JOUR
T1 - Increased soluble CD44 concentrations are associated with larger tumor size and lymph node metastasis in breast cancer patients
AU - Mayer, Sebastian
AU - Zur Hausen, Axel
AU - Watermann, Dirk Otto
AU - Stamm, Stefan
AU - Jäger, Markus
AU - Gitsch, Gerald
AU - Stickeler, Elmar
N1 - Funding Information:
Acknowledgments This work was supported by a grant of the Deutsche Krebshilfe to E. S. (No. 107690)
PY - 2008/11
Y1 - 2008/11
N2 - 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).
AB - 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).
KW - Lymph node metastasis
KW - Primary breast cancer
KW - Soluble CD44
KW - Tumor size
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U2 - 10.1007/s00432-008-0397-z
DO - 10.1007/s00432-008-0397-z
M3 - Article
C2 - 18438684
AN - SCOPUS:53749085227
SN - 0171-5216
VL - 134
SP - 1229
EP - 1235
JO - Journal of Cancer Research and Clinical Oncology
JF - Journal of Cancer Research and Clinical Oncology
IS - 11
ER -