epidermal-growth-factor and Gliosarcoma

Cancer stem cells are defined as a subpopulation of cancer cells with the capacity to self-renew and differentiate, which may play critical roles in tumor initiation, progress and resistance to current treatments. It has been reported that Dendritic cells (DCs) transfected with total tumor RNA could induce strong antitumor T-cell responses both in vivo and in vitro. In the study, we investigated the characteristics of 9L tumor spheres, and evaluated the antitumor effects of DCs transfected with 9L tumor spheres RNA in vivo. The results showed that 9L tumor spheres have the properties of cancer stem cells, and the majority of 9L cells were positive for CD133 and nestin. DCs transfected with 9L tumor spheres RNA can significantly inhibit glioma growth and prolong the survival of 9L glioma-bearing rats. These results demonstrated that 9L cancer stem like cells were enriched in tumor spheres, and they were a part of CD133+ cells, DCs transfected with cancer stem cells RNA may be an effective therapy for glioma.

Topics: AC133 Antigen; Animals; Antigens, CD; Brain Neoplasms; Cancer Vaccines; Cell Culture Techniques; Cell Line, Tumor; Culture Media; Dendritic Cells; Epidermal Growth Factor; Fibroblast Growth Factor 2; Gliosarcoma; Glycoproteins; Interferon-gamma; Intermediate Filament Proteins; Kaplan-Meier Estimate; Neoplastic Stem Cells; Nerve Tissue Proteins; Nestin; Peptides; Rats; RNA; Transfection; Xenograft Model Antitumor Assays

We have previously documented that the vast majority of high-grade gliomas over-express binding sites for interleukin 13 (IL13) in situ. We now extend this analysis to evaluate the distribution of the binding of IL13 among other brain tumors. Tumor specimens from patients with low-grade gliomas, oligodendrogliomas, ependymomas, pilocytic astrocytomas, gliosarcomas, medulloblastomas, meningiomas, and metastases to the brain were analyzed and compared to a new series of glioblastoma multiforme (GBM) samples. Serial tumor tissue sections were incubated with 125I-labeled (i) IL13, (ii) antibody against transferrin (Tf) receptor, and (iii) epidermal growth factor (EGF). Most (17/18) GBMs stained specifically for IL13 binding sites while sections from 3/11 low-grade gliomas, 5/5 high-grade gliomas (grade III), 3/5 oligodendrogliomas (all three were anaplastic), and 1/2 gliosarcomas also showed specific binding for IL13. We did not detect IL13 binding sites in medulloblastomas (0/4) and found them only in 2/20 meningiomas. Metastases to the brain (4/12, i.e., lung adenocarcinomas and renal cell carcinoma) showed some binding of 125I-IL13. The presence of receptors for Tf was ubiquitous among all studied tumors while EGF receptor expression was much more variable. Since it appears that primarily the least differentiated forms of gliomas possess IL13 binding sites in abundance, it is plausible that IL 13 receptor expressed in low-grade gliomas might be a prognostically significant marker associated with their progression to high-grade gliomas. Finally, we demonstrate that the glioma-associated IL13 receptor is truly more restrictive in nature also due to its selective representation among brain tumors of glial origin.

Topics: Adenocarcinoma; Biomarkers, Tumor; Brain Neoplasms; Carcinoma; Cell Transformation, Neoplastic; Disease Progression; Ependymoma; Epidermal Growth Factor; ErbB Receptors; Gene Expression Regulation, Neoplastic; Glioma; Gliosarcoma; Humans; Interleukin-13; Interleukin-13 Receptor alpha1 Subunit; Interleukin-4; Medulloblastoma; Meningeal Neoplasms; Meningioma; Neoplasm Proteins; Oligodendroglioma; Receptors, Interleukin; Receptors, Interleukin-13; Receptors, Transferrin; Recombinant Proteins; Substrate Specificity