Glycans as biomarkers for cancer?

June 26, 2017

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 cells 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 tumor 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 tissue and the healthy one and found characteristic proteins up- or downregulated in the cancer tissue. 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.
-end-
About the Author

Dr. Carolyn Bertozzi is the Anne T. and Robert M. Bass Professor of Chemistry and Professor of Chemical and Systems Biology and Radiology (by courtesy) at Stanford University, and an Investigator of the Howard Hughes Medical Institute. Her research group studies cell surface interactions that contribute to human health and disease, using the techniques of organic synthesis, genetics, and biochemistry. Prof. Bertozzi has been recognized with many honors and awards for both her research and teaching accomplishments.

http://chemistry.berkeley.edu/faculty/chem/bertozzi

Wiley

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.