Untersuchung von CD24 als therapeutisches Zielmolekül für die Prävention der Progression im Brustkrebs
Hämatologie, Onkologie
Zellbiologie
Zusammenfassung der Projektergebnisse
CD24 is a small mucin-like, highly glycosylated cell surface protein that is over-expressed in various types of human malignancies, including breast cancer (BC). Studies have associated CD24 with pro-tumorigenic signaling, motility, survival and metastasis progression. In BC, tumor-initiating cells have been defined by expression of cell surface markers as CD44high and CD24low/neg. Although, many breast tumors show high expression levels of CD24 that strikingly is correlated with a poor prognosis. These findings imply that CD24 might be important for the outgrowth of breast tumors but almost nothing is known about the transition between the CD24low, tumor-initiating state and the CD24high, more differentiated state in tumors and metastases and how these transitions are regulated on the physiological level. During our investigations we could demonstrate that glucocorticoids (GCs) have the ability to modulate the proportion of CD24+/CD24- cells in BC cell lines and display phenotypic and molecular characteristics of altered cellular states of differentiation. Furthermore, CD24-subpopulations correlated with expression of the glucocorticoid receptor (GR) explaining responsiveness to GCs and were susceptible to selective inhibitor treatments. Most strikingly, otherwise indolent BC cells acquired tumor-forming abilities in vivo. On the other hand outgrowth of aggressive BC cells was diminished by treatment with various GCs. In both mouse models tumor outgrowth was associated with expression of CD24. Future experiments might give detailed insight into the mechanism and importance of GC-driven CD24 regulation in tumor cells and the long-term consequences of GC usage as therapy standard in oncological treatment regiments.
