Glycans as biomarkers for cancer?

June 26, 2017, Wiley
Credit: Wiley

Glycosylated proteins are often overexpressed in tumor cells and thus could serve as tumor markers, especially those with the interesting molecule sialic acid as their sugar moiety. In the journal Angewandte Chemie, American scientists now report on a bioorthogonal labeling test for sialylated glycoproteins based on a glycoproteomics approach. This assay not only assesses the level of sialylated glycans in the tumor cell membranes, but also identifies up- or downregulated proteins directly in the prostate cancer tissue.

Tumor are characterized by an accelerated metabolism with some proteins up- and some downregulated compared to cells in normal healthy tissue. As the quantity and quality of proteins in the cells can be assessed by a proteomics approach, scientists seek to use a proteomics test system to identify and explore the proteins typical for cancer metabolism. Carolyn R. Bertozzi and her research team from Stanford University have chosen a bioorthogonal labeling strategy to identify sialylated glycoproteins, which are especially interesting because the sialic acid sugar moiety helps cells to evade the immune system. Their labeling approach further applies the cancer tissue, not cell cultures, thus it provides direct assess to the tumor metabolism in its natural environment.

In bioorthogonal labeling, a label, usually a fluorescent molecule, is chemically attached to target molecules, which can then be identified by bioimaging or mass spectrometry. One of the key aspects is that there is as little interference with the normal cell metabolism as possible. "Accurate models of human biology are particularly important for research at the intersection of glycoscience and human health," the authors argue. Therefore, they chose tissue slice cultures as a form of live human tumor tissue, because "prostate tissue slice cultures ... allow direct comparisons of cancerous and normal tissue from the same patient source."

In their approach, the tissue slice cultures were treated with an azide-modified sialic acid, which was readily integrated into the cell metabolism. Then, a fluorescent label was chemically attached to the azide group. After the labeling, the scientists inspected the tissue slices either directly by imaging or by mass spectrometry after cell lysis. They observed clear differences between the cancer and the healthy one and found characteristic proteins up- or downregulated in the . Merging this platform with existing glycoproteome analysis techniques are future options, the authors propose, setting the stage for addressing further questions related to the roles of sialic acid, glycoproteins, and cancer.

Explore further: Tumor-targeting system uses cancer's own mechanisms to betray its location

More information: David R. Spiciarich et al, Bioorthogonal Labeling of Human Prostate Cancer Tissue Slice Cultures for Glycoproteomics, Angewandte Chemie International Edition (2017). DOI: 10.1002/anie.201701424

Related Stories

Blocking obesity with a protein-sugar combination

January 10, 2017

Researchers at the RIKEN-Max Planck Joint Research Center for Systems Chemical Biology in Japan have discovered an enzyme that can prevent obesity in mice. Published in the Journal of Biological Chemistry, the study shows ...

Researchers investigate 59 tumor cell lines

August 8, 2013

In what is the biggest study of its kind to date, researchers from Technische Universität München (TUM) have identified over 10,000 different proteins in cancer cells. "Nearly all anti-tumor drugs are targeted against cellular ...

Recommended for you

A decade on, smartphone-like software finally heads to space

March 20, 2019

Once a traditional satellite is launched into space, its physical hardware and computer software stay mostly immutable for the rest of its existence as it orbits the Earth, even as the technology it serves on the ground continues ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.