Related Experiment Video

Updated: Apr 26, 2026

A Novel High-resolution In vivo Imaging Technique to Study the Dynamic Response of Intracranial Structures to Tumor Growth and Therapeutics
12:09

A Novel High-resolution In vivo Imaging Technique to Study the Dynamic Response of Intracranial Structures to Tumor Growth and Therapeutics

Published on: June 16, 2013

14.8K

Linking tumor hypoxia with VEGFR2 signaling and compensatory angiogenesis: Glycans make the difference

Diego O Croci1, Gabriel A Rabinovich2

  • 1Laboratorio de Inmunopatología; Instituto de Biología y Medicina Experimental (IBYME); Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET); Buenos Aires, Argentina.

Oncoimmunology
|August 13, 2014
PubMed

Insights

Tumor cells can develop resistance to anti-VEGF cancer treatments. Galectin-1 binding to VEGFR2, triggered by low oxygen, promotes blood vessel growth and tumor regrowth despite VEGF blockade.

Area of Science:

  • Molecular Oncology
  • Cancer Angiogenesis
  • Glycobiology

Background:

  • Vascular Endothelial Growth Factor (VEGF) signaling blockade shows clinical benefit in some cancers.
  • Tumor regrowth after anti-VEGF therapy indicates the activation of compensatory angiogenic pathways.
  • Understanding resistance mechanisms is crucial for improving anti-angiogenic cancer treatments.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying tumor resistance to VEGF blockade.
  • To identify key players involved in compensatory angiogenesis during anti-VEGF therapy.
  • To elucidate the role of galectin-1 and N-glycans in VEGFR2 signaling under hypoxia.

Main Methods:

  • Analysis of tumor samples from patients treated with anti-VEGF agents.
  • Biochemical assays to study the interaction between galectin-1, N-glycans, and VEGFR2.
  • Cellular and in vivo models to assess the impact of galectin-1 on angiogenesis under hypoxic conditions.

Main Results:

  • Galectin-1 associates with complex N-glycans on Vascular Endothelial Growth Factor Receptor 2 (VEGFR2).
  • This association links tumor hypoxia to sustained VEGFR2 signaling.
  • Galectin-1-mediated signaling preserves angiogenesis even when VEGF is blocked, promoting tumor regrowth.

Conclusions:

  • Galectin-1-N-glycan interactions on VEGFR2 represent a critical compensatory mechanism in anti-VEGF therapy resistance.
  • Targeting the galectin-1-VEGFR2 axis may overcome resistance and enhance the efficacy of VEGF-targeted cancer treatments.
  • This finding offers a novel therapeutic strategy for improving outcomes in patients with refractory angiogenesis-dependent tumors.
Keywords:
angiogenesisanti-VEGFcancer immunotherapygalectinglycansglycosylationinflammation

More Related Videos

Isolation and Culture Expansion of Tumor-specific Endothelial Cells10:15

Isolation and Culture Expansion of Tumor-specific Endothelial Cells

Published on: October 14, 2015

10.6K
Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells09:03

Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells

Published on: November 23, 2014

9.2K

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...
2.9K
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...
6.3K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.7K
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...
6.3K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.6K
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...
8.1K