CD24 Promotes Invasion of Glioma Cells In Vivo

Abstract

Based on the hypothesis that adhesion molecules expressed on the surface of glioma cells mediate brain invasion, we examined the effect of CD24 on growth and migration of gliomas in vitro and in vivo. CD24, a glycosylphosphatidylinositol anchored, highly glycosylated adhesion molecule, is expressed in hematopoietic and neural cells. We found immunohistochemical expression of CD24 in human glioblastomas. We then established a clone from C6 rat glioblastoma cells, where mouse CD24 (also called heat stable antigen) is under control of a tetracycline-responsive promoter. In the presence of tetracycline (1 microg/ml) CD24 was downregulated by 20-fold. In vitro migration assays were performed on a basement membrane preparation (matrigel) and on myelin, the main substrates of in vivo glioma migration. While the cells were more motile on matrigel as compared with myelin, no relation between CD24 expression and motility was observed. We then transplanted the C6 clone into the striatum of nude mice and regulated CD24 expression via tetracycline in the drinking water (1 mg/ml). After 3 weeks, CD24 positive tumors of mice getting no tetracycline showed diffuse invasion of tumor cells in a brain area 10-fold larger than in CD24-suppressed tumors of mice receiving tetracycline. These data show that CD24 stimulates migration of gliomas in vivo and they suggest a role for this adhesion molecule in diffuse brain invasion of human gliomas.

Gene expression profiles in primary ovarian serous papillary tumors and normal ovarian epithelium: Identification of candidate molecular markers for ovarian cancer diagnosis and therapy

“…[41][42][43][44][45][46] However, it is only recently that CD24 overexpression has been reported at the RNA level in ovarian cancer. 4 Consistent with this report, we found the CD24 gene to be 14-fold differentially expressed in OSPC compared to NOVA.…”

CD24 is an independent prognostic marker of survival in nonsmall cell lung cancer patients

“…CD24 is expressed in a large variety of human tissues: physiologically, in developing or regenerating tissues (Figarella-Branger et al, 1993;Shirasawa et al, 1993;Poncet et al, 1996;Cram et al, 1999) and a few mature cell types such as, for example, granulocytes, keratinocytes (Redondo et al, 1998) and renal tubules (Droz et al, 1990). Pathologically, CD24 has been described in B-cell neoplasia (Pirucello and Lang, 1990;Raife et al, 1994;Lavabre-Bertrand et al, 1994), renal cell carcinoma (Droz et al, 1990), small cell lung cancer (Jackson et al, 1992), nasopharyngeal carcinoma (Karran et al, 1995), hepatocellular carcinoma (Huang and Hsu, 1995), bladder carcinoma (Gromova et al, 1999), glioma (Senner et al, 1999), breast cancer (Fogel et al, 1999;Liu and Vadgama, 2000) and ovarian cancer (Welsh et al, 2001;Kristiansen et al, 2002). This ubiquitous expression obviously excludes a diagnostic use of CD24 as a specific marker for NSCLC or any other tumour type.…”

“…It is a small heavily glycosylated mucin-like glycosyl-phosphatidylinositol(GPI)-linked cell surface protein (Pirruccello and Le Bien, 1986;Fischer et al, 1990;Akashi et al, 1994), which is physiologically expressed not only in developing (Shirasawa et al, 1993;Poncet et al, 1996;Cram et al, 1999) or regenerating (Figarella-Branger et al, 1993) tissue, but also in granulocytes, pre-B-cells, keratinocytes (Redondo et al, 1998) and renal tubules (Droz et al, 1990). In neoplasia, CD24 expression has been described not only in haematologic malignancies (Pirruccello and Lang, 1990;Raife et al, 1994;LavabreBertrand et al, 1994), but also in a large variety of solid tumours, for example, renal cell carcinoma (Droz et al, 1990), small cell lung cancer (Jackson et al, 1992), nasopharyngeal carcinoma (Karran et al, 1995), hepatocellular carcinoma (Huang and Hsu, 1995), bladder carcinoma (Gromova et al, 1999), glioma (Senner et al, 1999), breast cancer (Fogel et al, 1999;Yang et al, 1999;Liu and Vadgama, 2000) and ovarian cancer (Welsh et al, 2001;Kristiansen et al, 2002). CD24 is a ligand of P-selectin (Sammar et al, 1994), an adhesion receptor on activated endothelial cells and platelets, and could thus contribute to the metastasising capacities of CD24-expressing tumour cells (Aigner et al, 1995(Aigner et al, , 1997(Aigner et al, , 1998Friederichs et al, 2000).…”

CD24: from A to Z

“…CD24 is broadly overexpressed on many types of tumor tissues, 60,84 including B-cell lymphomas, 85 erythroleukemia, 22 gliomas, 86 small cell lung cancer, 87 esophageal squamous cell carcinoma, 88 hepatocellular carcinoma, 89 cholangiocarcinoma, 90,91 pancreatic adenocarcinoma, 92 urothelial carcinoma, 93,94 ovarian cancer, 95 breast cancer, 28,96,97 primary neuroendocrine carcinomas 98 and prostate carcinomas. 99 Human cancer stem cells appear to have decreased expression of CD24 compared to their offspring; 100,101 however, it is unclear if the same pattern holds in mice.…”