Modulation of soluble CD44 concentrations by hormone and anti-hormone treatment in gynecological tumor cell lines

Serum levels of CD44 (sCD44) are increased in a variety of human diseases including gynecological malignancies showing hormone-dependent growth and proliferation. Very little is known about the mechanisms underlying the processing of soluble CD44 and influencing its release. Due to their major impact on gene transcription and cell proliferation steroid hormones or their antagonists might influence sCD44 processing. We investigated the effects of different hormonal conditions on overall soluble CD44 (sCD44std) concentrations in a subset of gynecological tumor cell lines. Established human breast and endometrium cancer cell lines were characterized for their membrane-bound CD44 protein, CD44 mRNA expression and steroid receptor status prior and after incubation with 17β estradiol (E2), medroxyprogesterone acetate (MPA), 4-hydroxy-tamoxifen (4-OH-Tam) and the gonadotropin releasing hormone (GnRH) agonist busereline. An enzyme linked immuno-sorbent assay (ELISA) using a monoclonal antibody directed against an epitope common to all CD44 isoforms was used to determine sCD44 levels in the supernatants of the tested cell lines. Interestingly, a strong correlation between sCD44 levels and the receptor status of the cells was seen. However, membrane-bound CD44 expression was not influenced by the hormonal environment. Our results indicate that distinct steroid hormones can specifically influence concentrations of soluble CD44. How this effect is involved in the tumorigenesis of gynecological malignancies and whether it might contribute to the biological behavior of special tumors should be investigated in further studies.