Nav: Home

First of its kind cancer stem cell research unlocks clues to treatment resistance

January 17, 2017

Researchers at Trinity College Dublin have made exciting new findings that could offer a means of fighting resistance to treatment for people with oesophageal cancer. Resistance to radiotherapy is a major stumbling block in the treatment of this cancer.

For the first time, the research team led by Dr Stephen Maher, Ussher Assistant Professor in Translational Oncology at Trinity, have discovered that a molecule lost from cancer stem cells, called miR-17, is important in driving oesophageal tumour resistance to radiotherapy.

The team of scientists, which incorporated specialists from Trinity, St. James's Hospital Dublin, the Coombe Women and Infant's University Hospital and the University of Hull in the UK, demonstrated that populations of tumour cells that had higher numbers of cancer stem cells formed larger, more aggressive tumours. They also demonstrated that the cancer stem cells were more resistant to radiation-induced cell death.

The findings from this ground breaking research were recently published in the international peer-reviewed journal Oncotarget.

Many oesophageal cancer patients receive radiotherapy and chemotherapy to shrink their tumour prior to surgery and this forms a key part of their treatment. Unfortunately, while a subset of patients have excellent responses to treatment, the majority of patients are actually resistant to various degrees, and are subjected to treatment side effects and an unnecessary delay to surgery, which can worsen their overall prognosis. To date there hasn't been a way to test which patients will respond well to radiotherapy or to reduce resistance to radiotherapy.

Cancer stem cells are a tiny population of tumour cells that exist inside most tumours, and acquire some of the features of normal stem cells. Normal stem cells are unspecialised cells that can be characterised by the ability to change into mature, specialised cells, like the normal cells that make up the normal oesophagus. When normal tissues are damaged, through injury for example, stem cells in the local environment, help to repopulate and rebuild the normal tissue. However, in a tumour, cancer stem-like cells, the tumour cells that have acquired stem cell-like abilities, are able to drive and maintain the growth of tumours and repopulate the tumours following the damage caused by radiotherapy and chemotherapy.

"This work is extremely important in understanding why tumours are inherently resistant to radiotherapy, and how they can acquire resistance. Our findings strongly suggest that it is the cancer stem cell population that we need to destroy if treatment is going to be effective in our oesophageal cancer patients", said Dr Maher.

"Up until recently cancer stem cells were largely considered hypothetical, as there were no clear ways to identify and isolate them. In this study we spent a tremendous effort in identifying tumour cells that had biological markers normally characteristic of stem cells. Once we had identified these stem-like tumour cells, we isolated them and started to pick apart their biology", continued Dr Maher.

The work, predominantly performed by Dr Niamh Lynam-Lennon, an Irish Research Council-funded Senior Research Fellow with Trinity's Department of Surgery, showed that the population of cancer stem cells could be further broken down into smaller groups, which had distinct radiation sensitivity profiles. Further genetic analysis revealed that the levels of a powerful gene-regulating molecule, called miR-17, were particularly low in the cancer stem cells that were most resistant to radiation. In patient samples, miR-17 was found to be much lower in the tumours of patients who did not respond to treatment.

"Interestingly, in the lab we found that if we put a synthetic version of miR-17 into the resistant cells they became more sensitive to radiation. Going forward, we could use synthetic miR-17 as an addition to radiotherapy to enhance its effectiveness in patients - this is a real possibility as a number of other synthetic miR-molecules are currently in clinical trials for treating other diseases", said Dr Lynam-Lennon.

Oesophageal adenocarcinoma, a cancer of the food-pipe, is a major problem in Ireland, the UK and the rest of the western world. Its incidence has increased by 600% over the past three decades, representing the largest increase in incidence of any disease of any kind over the same time period, and rates are projected to continue increasing over the next 20 years.
-end-
The work was largely funded by the Health Research Board (HRB) and involved research on cells grown in the lab, in vivo research and tumour samples from oesophageal cancer patients.

The paper is available here.

Trinity College Dublin

Related Stem Cells Articles:

More selective elimination of leukemia stem cells and blood stem cells
Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia.
Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.
First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.
Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.
The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.
Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.
New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.
NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.
Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.
In mice, stem cells seem to work in fighting obesity! What about stem cells in humans?
This release aims to summarize the available literature in regard to the effect of Mesenchymal Stem Cells transplantation on obesity and related comorbidities from the animal model.
More Stem Cells News and Stem Cells Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Our Relationship With Water
We need water to live. But with rising seas and so many lacking clean water – water is in crisis and so are we. This hour, TED speakers explore ideas around restoring our relationship with water. Guests on the show include legal scholar Kelsey Leonard, artist LaToya Ruby Frazier, and community organizer Colette Pichon Battle.
Now Playing: Science for the People

#569 Facing Fear
What do you fear? I mean really fear? Well, ok, maybe right now that's tough. We're living in a new age and definition of fear. But what do we do about it? Eva Holland has faced her fears, including trauma and phobia. She lived to tell the tale and write a book: "Nerve: Adventures in the Science of Fear".
Now Playing: Radiolab

Uncounted
First things first: our very own Latif Nasser has an exciting new show on Netflix. He talks to Jad about the hidden forces of the world that connect us all. Then, with an eye on the upcoming election, we take a look back: at two pieces from More Perfect Season 3 about Constitutional amendments that determine who gets to vote. Former Radiolab producer Julia Longoria takes us to Washington, D.C. The capital is at the heart of our democracy, but it's not a state, and it wasn't until the 23rd Amendment that its people got the right to vote for president. But that still left DC without full representation in Congress; D.C. sends a "non-voting delegate" to the House. Julia profiles that delegate, Congresswoman Eleanor Holmes Norton, and her unique approach to fighting for power in a virtually powerless role. Second, Radiolab producer Sarah Qari looks at a current fight to lower the US voting age to 16 that harkens back to the fight for the 26th Amendment in the 1960s. Eighteen-year-olds at the time argued that if they were old enough to be drafted to fight in the War, they were old enough to have a voice in our democracy. But what about today, when even younger Americans are finding themselves at the center of national political debates? Does it mean we should lower the voting age even further? This episode was reported and produced by Julia Longoria and Sarah Qari. Check out Latif Nasser's new Netflix show Connected here. Support Radiolab today at Radiolab.org/donate.