Angiogenesis can be reduced without significant reduction of tumor growth

Asa Svensson1, Ulrika Bäckman, Dieter Fuchs

  • 1Department of Medical Cell Biology, Children's Hospital, Uppsala University, Sweden.

Anticancer Research
|January 30, 2008
PubMed
Abstract

Insights

The angiogenesis inhibitor TNP-470 reduced blood vessel formation in neuroblastoma tumors in mice. However, significant tumor growth reduction and apoptosis were not observed, suggesting a need for more potent inhibition.

Area of Science:

  • Oncology
  • Cancer Research
  • Pharmacology

Background:

  • High-risk neuroblastoma (NB) has a poor 5-year survival rate (~50%).
  • Novel therapeutic strategies, including angiogenesis inhibition, are crucial for improving NB patient outcomes.

Purpose of the Study:

  • To evaluate the efficacy of the angiogenesis inhibitor TNP-470 in a mouse model of human neuroblastoma.
  • To assess the impact of TNP-470 on tumor angiogenesis, proliferation, apoptosis, and plasma levels of key growth factors.

Main Methods:

  • Nude mice with subcutaneous human neuroblastoma xenografts were treated with TNP-470 (30 mg/kg, every other day, subcutaneously).
  • Longitudinal plasma concentrations of vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF-2), and hepatocyte growth factor (HGF) were measured.
  • Tumor tissue slides were analyzed to quantify angiogenesis, proliferation, and apoptosis.

Main Results:

  • TNP-470 significantly inhibited angiogenesis, evidenced by reduced vessel length and surface area per tumor volume.
  • No significant effects on overall tumor growth, tumor cell proliferation, or apoptosis were observed.
  • Plasma concentrations of VEGF-A per tumor volume increased significantly following TNP-470 treatment.

Conclusions:

  • Angiogenesis inhibition requires reaching a critical threshold to induce significant tumor cell apoptosis and reduce tumor growth rate.
  • Further research is needed to optimize anti-angiogenic strategies for neuroblastoma treatment.

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation 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...
Mechanism of Angiogenesis01:10

Mechanism 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...
Cancer Therapies02:49

Cancer Therapies

Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...