Project Details
Abstract
Gliomas are solid tumors that originate from glial cells in the brain or spine. Gliomas account
for 81% of malignant brain tumor and the five-year survival rates post diagnosis of the most
common and aggressive glioma, glioblastoma (GBM) is only 5%. The patient survival and tumor
recurrent rates are closely correlated with tumor grades. However, it’s hard to accurately classify
gliomas just based on several molecular markers or tissue histology. While the progression
processes of some popular cancers are well-defined, the causes of gliomas are still unrevealed.
Searching for new grading and prognostic factors and development of new therapies and therapeutic
targets are imperative in glioma treatments. IGFBP3 belongs to the IGFBP family and was first
recognized as a binding partner of insulin-like growth factors (IGFs), stabilized circulating IGFs,
and prevented IGF binding with insulin-like growth factor receptors. Recently, more studies have
shown that IGFBP3 can bind to not only IGFs but extracellular matrixes, cell surface receptors, and
transcription factors. The roles of IGFBP3 in cancers are ambiguous, it may function as a tumor
suppressor or an enhancer depended on the cancer types. In gliomas, the protein and mRNA
expression of IGFBP3 is elevated and associated with increased tumor grade and poor survival of
glioma patients. However, the real functions of IGFBP3 in glioma cells and the underlying
molecular mechanisms of IGFBP3-regulated tumor progression are unclear. In the first year, we will
focus on the IGFBP3 protein and RNA expression in glioma patient tissues from the Chang-Gung
Memorial Hospital, also its correlation with clinicopathological characteristics and patient survival.
Next, we will investigate the IGFBP3 expression in blood vessels and its expression correlation
with angiogenic factors. Because we found that IGFBP3 knockdown suppressed cell growth, caused
cell cycle arrest at G1 phase, and inhibited Rb phosphorylation in U-87 MG cells, we will focus on
the effect of IGFBP3 expression on cell proliferation and cell cycle progression in at least 4
different glioma cells. Also, we will try to investigate the underlying molecular mechanism that
caused cell cycle arrest at G1 phase and prepare the IGFBP3 stable overexpression and knockdown
cells for in vivo mouse xenograft models. In the final year, we will search the alterations of RNA
expression associated with IGFBP3 expression using Affymetrix GeneChip® Human Genome
U133 Plus 2.0 Array and check the effect of IGFBP3 on in vivo cell growth using mouse xenograft
models. In this project, we will find the correlation between IGFBP3 expression and
clinicopathological factors also the angiogenic factors in gliomas patients in Taiwan. Furthermore,
we will examine the effect of IGFBP3 on cell growth in vivo and in vitro and try to reveal its
underlying molecular mechanisms using RNA microarrays screening and experiments focused on
cell cycle progression. IGFBP3 may be a good prognostic factor that predicts poor outcome of
glioma patients in Taiwan and a strong tumor enhancer as a potential therapeutic target in the future
glioma treatment.
Project IDs
Project ID:PC10701-0286
External Project ID:MOST105-2314-B182-019-MY3
External Project ID:MOST105-2314-B182-019-MY3
Status | Finished |
---|---|
Effective start/end date | 01/08/18 → 31/07/19 |
Keywords
- glioma
- IGFBP3
- cell cycle progression
- Rb phosphorylation
- angiogenesis
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