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 i ncluding gynecological malignancies showing hormone-dependent growth and pr oliferation. Very little is known about the mechanisms underlying the proce ssing of soluble CD44 and influencing its release. Due to their major impac t on gene transcription and cell proliferation steroid hormones or their an tagonists might influence sCD44 processing. We investigated the effects of different hormonal conditions on overall soluble CD44 (sCD44std) concentrat ions in a subset of gynecological tumor cell lines. Established human breas t and endometrium cancer cell lines were characterized for their membrane-b ound CD44 protein, CD44 mRNA expression and steroid receptor status prior a nd after incubation with 17 beta estradiol (E-2), medroxyprogesterone aceta te (MPA), 4-hydroxy-tamoxifen (4-OH-Tam) and the gonadotropin releasing hor mone (GnRH) agonist busereline. An enzyme linked immuno-sorbent assay (ELIS A) using a monoclonal antibody directed against an epitope common to all CD 44 isoforms was used to determine sCD44 levels in the supernatants of the t ested 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 ind icate that distinct steroid hormones can specifically influence concentrati ons of soluble CD44. How this effect is involved in the tumorigenesis of gy necological malignancies and whether it might contribute to the biological behavior of special tumors should be investigated in further studies.