Page 43 - AWSAR 2.0

During the process of MDR, some cancer cells (within the tumour population) can also form unique giant cells. Due to the prior exposure to drugs, these giant cells display some defects. They stall cytoplasmic division but continue with erroneous nuclear division, leading to the formation of multinucleated cells. These cells are, thus, also referred to as giant multinucleated cells (GMNCs) Fig1(b). GMNCs have been observed and correlated to the drug resistance in different types of cancers (breast, colon, cervical, brain, and others). Our research over the past few years with breast cancer has shown that the number of GMNCs increases three to five times during MDR. One of the unique features of GMNCs is that they can remain dormant for long periods and when the treatment subsides, they may divide (perform cytoplasmic division) to produce multiple daughter
cells. A study from other
research groups has shown that
these daughter cells can be of
different genetic variants, some
of which may lead to a more
aggressive form of cancer.
Moving further, we found that
these dormant GMNCs could
communicate with other cells
in their surroundings and
have serious consequences in
disease progression.
Communication by GMNCs
Cell-to-cell communication
is essential for the proper
functioning of any tissue. In
normal human tissue, cells communicate with each other to successfully perform specific functions and coordinate their death on ageing. Cancer cells, which are not normal to a human body, also communicate with other cells. But, because of their selfish nature, they work in their own interest rather than
Dr Aditya Parekh || 19
the interest of the organs or the body. They divide infinitely and do not die easily, thus disturbing the architecture and functioning of a tissue. Although it is an established fact that one cancer cell communicates with other cancer cells in its vicinity, the communication in the context of GMNCs has not been studied extensively. In the context of MDR, we have tried to observe how GMNCs communicate and influence other cancer cells (non-GMNCs) in their surroundings.
In our study published last year in the journal ‘Oncogene’, we found that GMNCs over-synthesized a variety of proteins and released them into their surroundings. A couple of proteins from that list, namely vascular endothelial growth factor (VEGF) and macrophage migration inhibitory factor (MIF), manipulated intracellular signal transduction
on the cells in their vicinity. Earlier, research from other groups had shown that VEGF and MIF could activate p44/42 intracellular signalling. P44/42 is a signalling pathway known to aid cells to divide, migrate and survive. In the present study, we found that VEGF and MIF secreted by GMNCs modulated the activity of p44/42 on their neighbouring cells. P44/42 activation led to the modulation of cell death proteins (or survival proteins), namely Bcl-2, Bad, Bcl-xL, and Bax. It acted on the cells (mainly non-GMNCs) and helped increase the levels of
anti-death proteins such as Bcl-XL and Bcl-2, and a decrease in the pro-death proteins such as Bax and Bad. Thus, it helped in providing survival advantages in the presence of drugs. On the whole, we observed that the dormant GMNCs could give out signals to other non- GMNCs cells and help in increasing their
Cancer cells, which are not normal to a human body, also communicate with other cells. But, because of their selfish nature, they work in their own interest rather than the interest of the organs or the body. They divide infinitely and do not
die easily, thus disturbing the architecture and functioning of a tissue.