Hemangioblastomas share protein expression with embryonal hemangioblast progenitor cell
Sven Gläsker1, Jie Li, John B Xia
1Surgical Neurology Branch, National Institutes of Neurological Disorders and Stroke, NIH, Bethesda, Maryland 20892, USA.
Cancer Research
|April 19, 2006
Summary
Hemangioblastoma stromal cells express embryonic progenitor markers, suggesting a hemangioblast origin. This finding may lead to new therapies for these central nervous system tumors.
Area of Science:
- Neuro-oncology
- Developmental Biology
- Tumorigenesis
Background:
- Hemangioblastomas are CNS tumors with unknown cell origins.
- Their neoplastic stromal cells hinder nonsurgical therapy development and biological understanding.
Purpose of the Study:
- To identify the cytologic origin of hemangioblastoma stromal cells.
- To elucidate potential autocrine stimulatory loops and topographical distribution mechanisms.
Main Methods:
- Immunohistochemical analysis of stromal cell protein expression.
- Identification of molecular signaling pathways involved in tumor growth.
Main Results:
- Stromal cells express proteins (Scl, brachyury, Csf-1R, Gata-1, Flk-1, Tie-2) characteristic of embryonic hemangioblast progenitors.
- A novel autocrine/paracrine loop involving Tie-2 and Ang-1 was identified.
- Consistent Scl expression may explain tumor distribution in the CNS.
Conclusions:
- Embryonic progenitors with hemangioblast potential are a likely cytologic origin for hemangioblastoma stromal cells.
- Autocrine loops, influenced by differentiation and HIF activation, are implicated in hemangioblastoma.
- Scl expression offers insights into the CNS topographical distribution of these tumors.
Related Concept Videos
01:24Regulation of Angiogenesis and Blood Supply
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
01:34Production of Formed Elements
Hemangioblasts are multipotent stem cells originating from the mesoderm. They give rise to hematopoietic stem cells (HSCs), which undergo hematopoiesis to produce all the formed elements of blood. This process is regulated by a complex network of hematopoietic growth factors, including transcription factors, growth factors, and cytokines. These factors stimulate the HSCs to divide and differentiate, though some HSCs remain undifferentiated to maintain a self-renewing pool.
Most HSCs commit to...
Most HSCs commit to...
01:21Hematopoiesis
The process of blood cell formation is called hematopoiesis. Hematopoiesis starts early during development, on the seventh day of embryogenesis. This phase of hematopoiesis is called the primitive wave, wherein the extraembryonic yolk sac allows the production of erythroid cells and endothelial cells from a common precursor called hemangioblast. The erythroid cells provide oxygen to support the growth of the rapidly dividing embryo. Hemangioblasts later develop into hematopoietic stem cells or...
01:19Multipotency of Hematopoietic Stem Cells
The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
01:10Mechanism of Angiogenesis
Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...