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Culprit That Increases Aggressiveness of Colorectal Cancer Identified

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  • The level of metabolite D-2-hydroxyglutarate (D-2HG), was higher in colorectal cancer cells.
  • D-2HG transformed cells by making them adhere less strongly to each other and causing them to migrate easily to other sites.
  • This suggests the importance of the metabolite in prognosis of colorectal cancer.

Culprit That Increases Aggressiveness of Colorectal Cancer Identified

A metabolite, D-2-hydroxyglutarate (D-2HG), that makes the colorectal cancer cells more invasive and increases its likelihood of spreading to other organs has been identified.

Cancer cells exhibit a range of properties which are different from the function of the normal cells in the body. There are also differences in the levels various metabolites in a normal cell and in a cancerous cell.


And it has not yet been determined whether such altered levels is a cause or consequence of the cancerous growth.

Incidence of Colorectal Cancer

In the developed countries it is the second most commonest cancer after lung cancer.

Incidence rates range from 25.3 per 100,000 in Eastern Europe to 45.8 per 100,000 in Australia. Incidence rates in India are quite low about 2 to 8 per 100,000.

Incidence of colorectal cancer is highest in developed countries such as the United States and Japan, and lowest in developing countries like Africa and Asia.

Incidence is slightly higher in men than women, and is highest in African American men.

New discovery

Researchers from the Osaka University in Japan have identified a metabolite, D-2-hydroxyglutarate (D-2HG), that causes the colorectal cancer cells to develop dangerous properties making them vicious and increasing its likelihood of metastasis or spreading to other organs.

Researchers hope that this breakthrough discovery offers hope for improved treatment of colorectal cancer.

How the researchers identified the function of the metabolite

The researchers studied many types of cancer cells and normal cells in the body. They identified that colorectal cancer cells had high levels of D-2-hydroxyglutarate (D-2HG) in them.

On administering D-2HG into cancer cells, it induced the cells to undergo transformation. D-2HG causes cell transformation by increasing the expression of a gene called ZEB1.

D-2HG causes the epithelial cells to transform to mesenchymal cells making it easier for the cancer cells to invade a local tissue, enter bloodstream and get transported to new sites to establish a tumor.

This transformation caused the cells to migrate easily by reducing the adherence to each other. This property is associated with cancer progression and spread.

"When we grew the cells with D-2HG on plates and measured their movement, they migrated further than untreated cells" lead author Hugh Colvin says. "Using a Matrigel assay that models the ability of cancer cells to enter local tissue, the D-2HG treated cells were also more invasive."

To confirm their findings, researchers obtained specimens from 28 human colorectal cancer patients and divided them into two groups based on the levels of D-2HG.

The patient group that had high levels of D-2HGgroup had more often suffered cancer spread to distant organs, compared to patients group with low levels of D-2HG which suggested the importance of D-2HG in patient prognosis.

"When cancer cells initially emerge, it can be difficult for them to survive and multiply because of the local conditions," coauthor Hideshi Ishii says. "D-2HG makes cancer cell survival more likely by causing them to transform from epithelial to mesenchymal cells, meaning that they can invade local tissue, enter the blood, and be transported elsewhere to establish a new tumor."

The role of the new molecule in cancer progression and prognosis could also make it a promising target for colorectal cancer treatments in future.


  1. Colorectal Cancer/Colon and Rectal Cancer - (//www.medindia.net/patients/patientinfo/colorectalcancer-incidence.htm)

Source: Medindia

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