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Published on: July 12, 2018
Cod glycopeptide with picomolar affinity to galectin-3 suppresses T-cell apoptosis and prostate cancer metastasis
Prasun Guha1, Engin Kaptan, Gargi Bandyopadhyaya
1Department of Biochemistry and Molecular Biology, Institute of Marine and Environmental Technology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Abstract:
Cancer metastasis and immune suppression are critical issues in cancer therapy. Here, we show that a β-galactoside-binding lectin [galectin-3 (gal3)] that recognizes the Thomsen-Friedenreich disaccharide (TFD, Galβ1,3GalNAc) present on the surface of most cancer cells is involved in promoting angiogenesis, tumor-endothelial cell adhesion, and metastasis of prostate cancer cells, as well as evading immune surveillance through killing of activated T cells. To block gal3-mediated interactions, we purified a glycopeptide from cod (designated TFD100) that binds gal3 with picomolar affinity. TFD100 blocks gal3-mediated angiogenesis, tumor-endothelial cell interactions, and metastasis of prostate cancer cells in mice at nanomolar levels. Moreover, apoptosis of activated T cells induced by either recombinant gal3 or prostate cancer patient serum-associated gal3 was inhibited at nanomolar concentration of TFD100. Because the gal3-TFD interaction is a key factor driving metastasis in most epithelial cancers, this high-affinity TFD100 should be a promising antimetastatic agent for the treatment of various cancers, including prostate adenocarcinoma.
Insights
A novel glycopeptide, TFD100, effectively blocks galectin-3 interactions, inhibiting cancer metastasis and immune suppression. This promising antimetastatic agent shows potential for treating various cancers, including prostate adenocarcinoma.
Area of Science:
- Oncology
- Immunology
- Biochemistry
Background:
- Cancer metastasis and immune suppression are significant challenges in cancer therapy.
- Galectin-3 (gal3), a lectin recognizing the Thomsen-Friedenreich disaccharide (TFD), is implicated in promoting cancer progression and immune evasion.
- Gal3's role in angiogenesis, tumor cell adhesion, metastasis, and T cell apoptosis highlights its therapeutic relevance.
Purpose of the Study:
- To investigate the role of galectin-3 (gal3) in prostate cancer metastasis and immune suppression.
- To identify and characterize a molecule that can block gal3-TFD interactions.
- To evaluate the therapeutic potential of the identified molecule as an antimetastatic agent.
Main Methods:
- Purification of a glycopeptide (TFD100) from cod with high affinity for galectin-3.
- In vitro and in vivo assays to assess TFD100's ability to block gal3-mediated angiogenesis, tumor-endothelial cell interactions, and prostate cancer metastasis in mice.
- Assessment of TFD100's effect on T cell apoptosis induced by gal3.
Main Results:
- TFD100 binds galectin-3 with picomolar affinity.
- TFD100 significantly inhibits gal3-mediated angiogenesis, tumor-endothelial cell adhesion, and prostate cancer metastasis in mouse models at nanomolar concentrations.
- TFD100 prevents gal3-induced apoptosis of activated T cells.
Conclusions:
- The galectin-3/Thomsen-Friedenreich disaccharide interaction is a critical driver of cancer metastasis and immune suppression.
- The high-affinity glycopeptide TFD100 is a potent inhibitor of galectin-3 functions.
- TFD100 represents a promising therapeutic candidate for antimetastatic treatment of various epithelial cancers, including prostate adenocarcinoma.
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