A type of pituitary tumour known as craniopharyngioma appears to
form via a different mechanism to that thought to occur in more
common tumours, according to research.
The novel findings, generated by a team led by the UCL
(University College London) Institute of Child Health, will be
further explored to better understand how cell signalling triggers
the growth of such tumours - the third most common brain tumour in
children - and whether new treatments could be devised to block
these signals.
The study used mouse models to investigate cells in the
pituitary gland which are thought to act as stem cells, in that
they give rise to all the different cell types in the gland.
Researchers used a genetic approach to follow these cells and the
'daughters' they produced, establishing that they did indeed
generate new hormone-producing cells across all the different
specialised types.
However, when the original cells acquired a genetic mutation
often found in the childhood tumour adamantinomatous
craniopharyngioma, instead of dividing uncontrollably to generate
the tumour, they sent signals to induce changes in nearby cells,
causing the latter to divide and give rise to the tumour. The team
now needs to determine how widespread this alternative
tumour-forming model is across the range of endocrine tumours and
cancers.
The pituitary gland, a small endocrine (hormone-producing)
organ, controls a multitude of functions in the body. Termed the
'Master Gland', it directs other organs and endocrine glands by
producing hormones that regulate blood sugar, blood pressure,
metabolism and growth in children, and also control the sex
hormones and thereby reproduction and sexual function.
Pituitary tumours arise in around one in 1,000 people. Most of
these tumours are adenomas, which usually respond well to surgery
and/or radiotherapy.
Craniopharyngioma, though much rarer, is the third most common
brain tumour in children. Craniopharyngioma can behave aggressively
and tends to infiltrate nearby structures such as the brain and
optic tracts, leading to severe and life-threatening side effects,
including blindness, severe obesity, sleep disorders and type 2
diabetes mellitus, which can result in a poor quality of life for
many patients.
The molecular mechanisms underlying most pituitary tumours have
remained unknown up to now; these tumours rarely contain cells
carrying mutations in the most commonly found oncogenes and tumour
suppressor genes critical in other human tumours and cancers. The
ICH study reveals a new possible mechanism which could explain how
pituitary tumours form.
Professor Mehul Dattani, Paediatric Endocrinologist at Great
Ormond Street Hospital said: "Craniopharyngiomas are currently
treated by removing most of the tumour surgically, and then giving
the patient radiotherapy. These tumours often recur and there is no
specific treatment targeting the mutated stem cells."
Dr Juan Pedro Martinez-Barbera, who led the research team at the
UCL Institute of Child Health, adds: "The next stage of our
research will be to better understand the mechanisms that take
place after the cells acquire the mutation which leads to them to
produce the tumour-promoting signals. Understanding what signals
these cells are releasing in the pituitary gland could help us to
find new treatments that specifically block the signals and prevent
or slow down the growth of the tumour.
"Advanced cancer can be very powerful, with cells having
developed multiple ways to evade the patient's immune system and
generate new cancer cells that are resistant to treatments. At the
initial stages of tumour formation, tumour cells are easier to
target and eliminate. Early diagnosis of cancer and new treatments
targeting tumour cells would help to boost survival rates as well
as reducing the damaging effects of both cancer and the intensive
treatments required to eradicate it."
The paper, Sox2+ Stem/Progenitor Cells in the Adult Mouse Pituitary Support
Organ Homeostasis and Have Tumor-Inducing Potential, is
published in Cell Stem Cell.