Science and Technology

Cancerous strategy

Preeti Mehra | Updated on August 29, 2021

Why a heterogeneous mix of rogue cells are more invasive than fixed formations

In the battle against cancer, any new understanding of the body’s rogue cells that invade nearby tissues and organs is significant. Researchers at the department of biosciences and bioengineering, IIT-Bombay, have found that cancer cells of different sizes and stiffness or flexibility are far more “migratory and invasive than a group of homogenous or uniform cells”.

Explains Dr Shamik Sen, associate professor, IIT-Bombay, who mentored the study: “It is now well established that each tumour is different from another.” Further, individual cells in a tumour can be distinct from each other in shape, size, stiffness, and so on.

This property of cancers, ‘tumour heterogeneity’, aids their spread. Heterogeneity enables cells to continuously re-position individual cells within a moving group of cells. This enhances the net invasiveness of the cell population, Sen says.

Using two types of breast cancer cell lines (cells that divide and grow under lab conditions) the IIT team analysed individual cell sizes, how they moved around, and their flexibility. Employing computer simulation, they mixed different types of cells in different proportions and observed how they invaded and how far each cell translocated or moved from its original place.

Translocation is more significant in an invasion than scattered movement of cells with no forward movement.

An article on IIT-Bombay’s website makes an analogy with football. Players may pass the ball around but fail to advance into the opposing team’s defence. Similarly, cells may move around agitatedly but without moving forward. A heterogeneous group of cells employs a strategy akin to “Total Football”, where players move freely, replacing each other’s position, thus maintaining the pressure of the attack.

Points out Dr Sen: “We observed that both differing sizes and stiffness was required to enhance invasion. Cells are constantly interacting with each other. They release and sense chemical signals to achieve this. During migration, as cells reposition themselves, some become leaders and the rest followers. Heterogeneity may allow better co-operation between the sub-populations, driving faster migration.”

It identified sub-populations based on cell size and stiffness, and one which closely resembles cancer stem cells — which are associated with increased invasiveness and reduced sensitivity to chemotherapy. Cells at the leading edge were found to be smaller and softer than the rest.

Will neutralising these attacker cells arrest cancer spread? Not really. Tumor cells are not only heterogeneous but also constantly evolving. Studies show that a sub-population grown in isolation can re-generate the entire population.

According to Dr Sen, even designing cell-based biomaterials to directly counter leader cells may not be a great idea. Reason: It is difficult to control stem cell proliferation and the type of cells it could give rise to once inside the body.

Also, it is now well known that stem cells can be transformed by cancer cells to further expedite cancer invasion. “Further work needs to be done in order to identify novel markers exclusive to attacker cells,” Sen says.

Preeti Mehra

Published on August 29, 2021

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