was led by Dr.
James Jackson, PhD, who is an Assistant Professor in the Department of
Biochemistry and Molecular Biology at the Tulane University School of Medicine,
New Orleans, Louisiana, USA
so that they cannot spread to other sites in
the body, which is technically termed as metastasis.
However, it may
also be administered for reducing the symptoms or prolonging life.
There are several
classes of chemotherapy drugs, based on their mechanism of action. Some
examples include the following:
such as doxorubicin damage the DNA
(deoxyribonucleic acid) of the cancer cells, thereby killing them. However, a
small proportion of these cancer cells may survive the initial course of
chemotherapy, which can give rise to relapsed tumors.
Tumor relapse is
especially a problem in case of breast cancer
, which retains a normal copy
of the TP53
gene that encodes the tumor
protein p53 (p53). The p53 protein is a
, which is responsible
for regulating cell division by preventing cells from dividing and
proliferating too fast or in an uncontrolled fashion.
The cancer cells that survive
the onslaught of chemo drugs are responsible for causing a relapse. These surviving cancer cells
generally stop proliferating and enter a dormant yet metabolically active state
of suspended animation known as senescence. Interestingly, these senescent
cancer cells produce copious amounts of inflammatory molecules and other
factors that promote tumor reactivation. Therefore, chemotherapy-treated breast
cancer patients having a normal copy of the TP53
gene are prone to relapse and have a poor survival rate.
properties of these senescent cancer cells that allow their survival after
chemotherapy treatment is extremely important,"
says Dr. Crystal A.
Tonnessen-Murray, a Postdoctoral Fellow in Jackson's laboratory at the Tulane
University School of Medicine, USA.
Uniqueness of the
The study is unique due to the fact that it has made a
ground-breaking discovery about the behavior of cancer cells, which was not
known before. The research
team found that breast cancer cells that
and enter into a phase of senescence, frequently
engulf adjacent cancer cells - a phenomenon akin to cannibalism
team was surprised to find that this cannibalistic behavior was not only
exhibited by cancer cells grown in cell culture in the laboratory, but also in
tumors growing in mice. The research team also discovered that lung and bone
cells that had undergone senescence were also capable of
engulfing their neighboring cancer cells.
It was further revealed that the senescent cancer cells
activated a group of genes that are also found in white blood cells (WBC),
which are responsible for engulfing pathogenic microbes or dead cellular
debris. Subsequently, these materials are degraded in cellular organelles known
as lysosomes, which have an acidic environment, thereby facilitating digestion.
Likewise, the senescent cancer cells, after 'eating' their neighboring cancer
cells, also digest the cellular debris within their lysosomes.
Implications of the Study
The phenomenon of
cannibalism that is exhibited by cancer cells helps them to stay alive.
Senescent cancer cells that engulfed a neighboring cancer cell survived
significantly longer in cell culture, compared to those that didn't exhibit
this cannibalistic behavior.
neighboring cancer cells could provide the senescent cancer cells with the
necessary energy resources for them to survive the attack of chemo drugs,
as well as produce
factors responsible for bringing about tumor relapse.
concludes: "Inhibiting this process may
provide new therapeutic opportunities because we know that it is the breast
cancer patients with tumors that undergo TP53-mediated senescence
in response to chemotherapy that have a poor response and poor survival rates."
The study was
funded by theUS Department of
Defense, Virginia, the National Institutes of Health (NIH), and the
NIH/National Institute of General Medical Sciences, Bethesda, Maryland, USA.
- Chemotherapy-induced senescent cancer cells engulf other cells to enhance their survival - (http://jcb.rupress.org/content/early/2019/09/16/jcb.201904051)