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IITG-IISc test mimics spread of breast cancer cells

By Staff Reporter

GUWAHATI, Aug 21 - The Indian Institute of Technology (IIT) Guwahati and the Indian Institute of Science (IISc) Bangalore have collaborated for an experiment to show how breast cancer cells spread through blood to other parts of the body.

The multidisciplinary and multi-institutional team seeks to bridge this gap in understanding and works towards unravelling the mechanisms involved in the growth and spread of breast cancer.

The research, led by Prof Siddhartha Ghosh from IIT Guwahati, Prof Gautam Biswas from IIT Guwahati, Dr Mohit Kumar Jolly from IISc Bangalore and Dr Amaresh Dalal from IIT Guwahati, together with a research fellow Dr Binita Nath and research scholars Anil Bidkar and Vikash Kumar, developed a PDMS-based complex flow passage with an overall diameter of 184 micrometres with built-in blockages at certain locations that reduce the effective flow passages with a diameter of 7 micrometres.

The complex flow passage mimics a capillary endothelial barrier followed by a capillary network. Their work has recently appeared in the Journal of Clinical Medicine, published from Switzerland.

Highlighting the importance of understanding how metastasis works, Prof Ghosh said, �While breast cancer starts as a local disease, the cancer can grow and spread to other organs, in a process called �metastasis�, which is the most devastating attribute of the disease. We do not yet fully know the molecular and cellular mechanisms of breast cancer metastasis, and this hinders the development of treatment protocols that can prevent or treat cancer spread.�

He said that human bodies are made up of billions of cells of various types and various types of cancers start from different types of cells and added that breast cancer starts in epithelial cells.

Epithelial cells are found in skin and as lining for all organs inside the body as well as body parts such as breast and the insides of the chest cavity.

It has been known that cancer cells migrate from their point of origin to other parts of the body by transforming into other types of cells. For example, the conversion of cancer-ridden breast epithelial cells into mesenchymal cells enables cell migration, invasion and drug resistance, and consequently, contributes to cancer spread and disease aggressiveness. The cancer-carrying mesenchymal cells can reconvert to epithelial cells at another site, causing secondary cancer.

Talking about the experimental model devised to study and bridge the gap in understanding this research, Prof Biswas said, �While the epithelial-to-mesenchymal transition (EMT) is known to be an important factor in cancer spread, how the converted cells travel through the blood vessels and undergo reverse transition (mesenchymal to epithelial) at the secondary sites has hitherto not been completely understood. Our effort was to understand how the cells lose their EMT phenotype and revert back to epithelial format through a process termed MET.�

This structure was designed to mimic broken membranes through which cancer cells find their way into the blood stream.

The PDMS passage was then connected to channels that mimicked network of blood vessels. The cells undergo EMT. The EMT cells are then brought back through the mimicked endothelium into the tissue compartments. The reversion process is termed as MET.

The movement of the cells through various sections of the complex micro-channel was captured using high-speed camera, and the videographs showed the ways in which cancer spread from one site to another, through such narrow passages.

The team found that the EMT cells had enhanced migratory properties and retained 50 per cent viability, even after migration through wells and constricted passages. They also found that the cells collected at the channel outlet regained epithelial character.

Among the most important observations made by the team was that the EMT cells were more resistant to drugs compared to the original epithelial cells and the reconverted epithelial cells.

�Our work is seminal in the area of cancer metastasis in that it explains the flow dynamics of the breast cancer cells and presents a vivid picture of EMT movement,� added Prof Ghosh.

Surveys have shown that breast cancer is the most prevalent form of cancer among Indian women, with 25.8 out of 1,00,000 women suffering from it.

It has been predicted that by 2020, there would be 18 lakh Indian women with breast cancer.

The new research was intended to highlight the need for inter-departmental and inter-institutional studies to understand cancer better and for the development of better screening programme and therapeutic protocols to manage this disease burden in future.

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IITG-IISc test mimics spread of breast cancer cells

GUWAHATI, Aug 21 - The Indian Institute of Technology (IIT) Guwahati and the Indian Institute of Science (IISc) Bangalore have collaborated for an experiment to show how breast cancer cells spread through blood to other parts of the body.

The multidisciplinary and multi-institutional team seeks to bridge this gap in understanding and works towards unravelling the mechanisms involved in the growth and spread of breast cancer.

The research, led by Prof Siddhartha Ghosh from IIT Guwahati, Prof Gautam Biswas from IIT Guwahati, Dr Mohit Kumar Jolly from IISc Bangalore and Dr Amaresh Dalal from IIT Guwahati, together with a research fellow Dr Binita Nath and research scholars Anil Bidkar and Vikash Kumar, developed a PDMS-based complex flow passage with an overall diameter of 184 micrometres with built-in blockages at certain locations that reduce the effective flow passages with a diameter of 7 micrometres.

The complex flow passage mimics a capillary endothelial barrier followed by a capillary network. Their work has recently appeared in the Journal of Clinical Medicine, published from Switzerland.

Highlighting the importance of understanding how metastasis works, Prof Ghosh said, �While breast cancer starts as a local disease, the cancer can grow and spread to other organs, in a process called �metastasis�, which is the most devastating attribute of the disease. We do not yet fully know the molecular and cellular mechanisms of breast cancer metastasis, and this hinders the development of treatment protocols that can prevent or treat cancer spread.�

He said that human bodies are made up of billions of cells of various types and various types of cancers start from different types of cells and added that breast cancer starts in epithelial cells.

Epithelial cells are found in skin and as lining for all organs inside the body as well as body parts such as breast and the insides of the chest cavity.

It has been known that cancer cells migrate from their point of origin to other parts of the body by transforming into other types of cells. For example, the conversion of cancer-ridden breast epithelial cells into mesenchymal cells enables cell migration, invasion and drug resistance, and consequently, contributes to cancer spread and disease aggressiveness. The cancer-carrying mesenchymal cells can reconvert to epithelial cells at another site, causing secondary cancer.

Talking about the experimental model devised to study and bridge the gap in understanding this research, Prof Biswas said, �While the epithelial-to-mesenchymal transition (EMT) is known to be an important factor in cancer spread, how the converted cells travel through the blood vessels and undergo reverse transition (mesenchymal to epithelial) at the secondary sites has hitherto not been completely understood. Our effort was to understand how the cells lose their EMT phenotype and revert back to epithelial format through a process termed MET.�

This structure was designed to mimic broken membranes through which cancer cells find their way into the blood stream.

The PDMS passage was then connected to channels that mimicked network of blood vessels. The cells undergo EMT. The EMT cells are then brought back through the mimicked endothelium into the tissue compartments. The reversion process is termed as MET.

The movement of the cells through various sections of the complex micro-channel was captured using high-speed camera, and the videographs showed the ways in which cancer spread from one site to another, through such narrow passages.

The team found that the EMT cells had enhanced migratory properties and retained 50 per cent viability, even after migration through wells and constricted passages. They also found that the cells collected at the channel outlet regained epithelial character.

Among the most important observations made by the team was that the EMT cells were more resistant to drugs compared to the original epithelial cells and the reconverted epithelial cells.

�Our work is seminal in the area of cancer metastasis in that it explains the flow dynamics of the breast cancer cells and presents a vivid picture of EMT movement,� added Prof Ghosh.

Surveys have shown that breast cancer is the most prevalent form of cancer among Indian women, with 25.8 out of 1,00,000 women suffering from it.

It has been predicted that by 2020, there would be 18 lakh Indian women with breast cancer.

The new research was intended to highlight the need for inter-departmental and inter-institutional studies to understand cancer better and for the development of better screening programme and therapeutic protocols to manage this disease burden in future.