Release Subtitle: Scientists show in-vivo and in-vitro how liver cancer stem cells are born, solving a central scientific mystery in this field
Release Summary Text:
Scientists have discovered how liver cancer spreads, but they haven’t
yet learned how liver cancer cells are born. A team of Okayama
University scientists has now established a model that demonstrates how,
given the right body environment and without genetic mutation, normal
stem cells can convert into cancer stem cells, which in turn proliferate
and cause the cancer tumor to grow. Their model could help develop
targeted drugs and therapies for liver cancer.
Full text of release:
Liver cancer is one of the deadliest cancers. It is insidious and does
not present symptoms until it has progressed considerably, at which
point, treatment options are limited and chances of survival are low.
The most common type of liver cancer is hepatocellular carcinoma (HCC).
HCC is most frequently seen in patients with chronic liver conditions
such as hepatitis B or C and cirrhosis, and it takes the lion’s share in
mortality rates from liver cancer.
Over the past two decades or so, research on liver cancer and cancer in
general has advanced with great strides. Scientists have found that all
cancer cells for a particular type of cancer are not alike. Among a set
of cancer cells, there is a rare subset of cells called cancer stem
cells (CSCs) which function similarly to normal stem cells in that they
are what cause cancer cells to form, renew, and proliferate. In a cancer
patient, if you resected a tumor and removed all other cancer cells but
left CSCs alive, the CSCs would cause the cancer to grow back. CSCs are
what sustain the cancer.
But what causes CSCs to form Research posits that normal stem cells
mutate into CSCs under specific body environmental and/or genetic
conditions. However, in the case of the liver, until recently, studies
were yet to confirm the particular conditions and triggers for this
conversion to CSCs, and whether these are environmental or genetic or
both.
Now, for the first time, a group of scientists from Okayama University,
led by Professor Masaharu Seno and Said Mohamed Abdelsabour Afify, has
been able to develop CSCs from a type of normal stem cells by merely
exposing them to what are believed to be favorable body environmental
conditions, without introducing any mutations or foreign genes. “This is
the world’s first successful establishment of a liver CSC model from
normal iPSCs without genetic manipulation,” Prof. Seno remarks.
Normal iPSCs, or normal induced pluripotent stem cells, are a type of
stem cell that can regenerate to develop into any type of human tissue,
given the right conditions. In their laboratory, Prof. Seno and team
placed iPSCs obtained from mice in a conditioned medium of HCC cell
lines (comprising a type of liver-cancer derived cells called Huh7
cells). These Huh7 cells secreted chemicals that cause inflammation,
creating an environment mimicking chronic inflammation in the liver.
This was expected to trigger the conversion of the iPSCs to liver CSCs.
To find out whether this conversion occurred, the scientists had to
evaluate in vivo whether the resultant cells formed malignant tumors.
So, they injected the cells into the livers of immunodefficient mice.
With high efficiency, after only 28 days of injection, the livers had
developed malignant tumors. In contrast, untreated iPSCs gave rise to
teratoma-like tumors with various germ layers, which were benign.
Observation and chemical assays revealed that a considerable proportion
of the cells of the malignant tumors had high nuclear-to-cytoplasmic
ratios and high proliferation rates. Further, in these cells, liver
cancer-associated markers such as alpha fetoprotein, glypican 3 and
carcinoembryonic antigen, were expressed. Thus, the cells they had
managed to develop from the iPSCs were not only confirmed CSCs, but also
confirmed liver CSCs.
This work shows that liver CSCs could be born from normal stem cells in
an environment of chronic inflammation without genetic mutation. It also
provides a model for how liver cancer cells could be metastasizing. A
model is a prerequisite for further scientific study. With the model
that this study establishes, more targeted drugs could be developed and
tested and perhaps, prevention techniques, such as tailored diets, can
be discovered.
The scientists plan to test their model using human-tissue-derived iPSCs
in future and adapt it to other human tissues in addition to liver
tissue. Speaking of his vision, Prof. Seno says: “The results of further
investigations will make liver cancer prevention, diagnosis, and
treatment surer and surer. Finally, one day, the number of liver cancer
patients in the world will reduce and the complete treatment of liver
cancer will be possible.” The journey to the future that Prof. Seno
envisions, begins here.
Release URL: https://www.eurekalert.org/pub_releases/2020-05/ou-nms052120.php
Reference:
Title of original paper: A novel model of liver cancer stem cells developed from induced pluripotent stem cells.
Journal: British Journal of Cancer
DOI: http://dx.doi.org/10.1038/s41416-020-0792-z
Contact Person: SENO Masaharu
E-mail: mseno(a)oakayama-u.ac.jp
For inquiries, please contact us by replacing (a) with the @ mark.
Website: http://www.cyber.biotech.okayama-u.ac.jp/senolab/index.html
Facebook Profile: https://www.facebook.com/seno.masaharu
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