Differences in sugar levels drive breast cancer invasion: IISc study

BENGALURU: A recent study by researchers at Indian Institute of Science shows that a specific sugar called 2,6-linked sialic acid (2,6-Sial) is expressed at different levels on the surface of different breast cancer cells.
“Malignant tumors are increasingly being understood and interpreted as ecosystems of heterogeneous cellular entities — a patchwork of cells that look and behave differently, and cooperate or compete with each other as the cancer spreads.Understanding the causes and consequences of such heterogeneity is a clear and present challenge for researchers,” an IISc statement read.
In the paper published in ACS Central Science, a peer-reviewed journal, a group led by Ramray Bhat, assistant professor, department of molecular reproduction, development and genetics, shows that cells showing higher levels of 2,6-Sial stick less strongly to their surroundings and, therefore, are less likely to invade through them.
On the other hand, cells showing moderate levels of 2,6-Sial adhered strongly and invaded more efficiently. Using an in-house 3D culture technique, the researchers reconstructed the tumor microenvironment on a dish to film the tumoroid – cluster of cancer cells – as it grows. Then, they separated the two cellular populations with different levels of 2,6-Sial, labelled them and then recombined them.
The team found that the cells with higher 2,6-Sial levels move slowly and form the central bulk of the tumoroid, whereas the ones with moderate levels move fast and form the invading front.
“The researchers then recreated the tumor in a computer model and simulated its spread. They show that having a slow-moving central bulk boosts the efficiency with which fast moving cancer cells can ‘unjam’ and spread outwards in a circular fashion, thereby justifying the need for heterogeneity,” the statement added.
This study, researchers said, deepened their understanding of a difficult problem in cancer biology and opened the doors to identifying insidious subpopulations within a crowded tumor environment.