Stem Cells In Human Pituitary Tumors

Written by Nestoras Mathioudakis, M.D.
Postdoctoral Fellow in Endocrinology

The pituitary gland, which is about the size of an almond, sits at the base of the skull and functions as the “master regulator” of the hormone system. It consists of two parts, the anterior and posterior pituitary. The anterior pituitary gland regulates the functions of multiple hormone-secreting glands in the body that control metabolism, reproductive function, growth and development, stress response, and lactation in women. The posterior pituitary plays an important role in regulating water balance in the body and releases the hormone oxytocin which stimulates uterine contractions during labor.


The anterior pituitary gland is a common site of tumor formation. Pituitary tumors are the third most common brain tumor; with recent studies suggesting that as many as 1 in 1000 people may have this kind of tumor. There are two main types of pituitary tumors: those that secrete excess hormones (“hormone-secreting”) and those that do not secrete any hormones (“non-functioning” tumors). Hormone-secreting tumors include: growth-hormone secreting tumors, prolactin-secreting tumors, ACTH-secreting tumors, and rare TSH-secreting tumors. Each of these tumor types can lead to a distinct clinical syndrome with recognizable signs and symptoms. While non-functioning tumors do not secrete excess hormones, they may decrease the blood levels of pituitary hormones resulting in a condition called “hypopituitarism.” In fact, even compression of the normal pituitary gland by hormone-secreting pituitary tumors can also lead to deficiencies of some pituitary hormones. Both types of pituitary tumors can also produce headaches and visual disturbances due to their close proximity to important brain structures, such as the optic chiasm.


The vast majority of pituitary tumors occur “sporadically,” that is, they are not passed down from generation to generation. Only a small fraction of pituitary tumors arise from genetic conditions, such as multiple endocrine neoplasia (MEN-1) or Familial Isolated Pituitary Adenomas (FIPA). While there has been extensive research in the field of pituitary tumor formation, we have not yet clearly been able to define how these tumors arise in individuals without inherited genetic mutations.
Recent evidence suggests that the adult pituitary gland may contain a population of progenitor or stem cells. We are investigating the possibility that pituitary tumors may also harbor a population of stem cells, which play a key role in tumor growth. We study pituitary tumor cell lines obtained from patients with pituitary tumors and compare these cells to normal pituitary cells obtained from autopsy cases of patients who died of other causes.


Aims/Goals


1.To see if a population of stem cells already characterized in the normal pituitary gland also exists in pituitary tumors.
2.To turn stem cells into all the cell types of the anterior pituitary gland.
3.To study the tumor-forming potential of isolated progenitor/stem cells injected into mice.


Current Progress


By growing pituitary cells in certain conditions, our team has identified several general stem cell markers in pituitary tumor cells. We are actively working to confirm the presence of specific stem cell markers already found in the normal pituitary gland. In addition, we are using a method to sort cells called FACS, which sorts cells according to the presence or absence of certain “stem cell” markers. We would like to see which population of cells grows more vigorously in vitro after sorting. We are also working to prove that these cells possess the cardinal features of stem cells, which include: 1) the ability to grow for long periods of time, or ideally indefinitely and 2) can be turned into all the cell types of the pituitary gland. Finally, we have injected mice with what we believe are the stem cells of a human pituitary tumor and will continue to study the tumor growth in these animals.


Clinical Implications/Relate to Patients


Even though pituitary tumors are non-cancerous tumors that rarely metastasize, they can be a source of significant health problems. Some tumors appear to behave more aggressively than others, and may come back after surgery, ultimately requiring a second surgery or radiation therapy. Despite years of extensive research in the field of pituitary tumor research, it is still unclear why pituitary tumors form, and why some tumors are more aggressive or resistant to treatment compared to others. If a stem cell population can be isolated from pituitary tumors, efforts can be made to study the unique cellular signaling pathways involved in controlling the growth of these cells. Ultimately, this information could shed light on potential targets in the cell cycle that could stop pituitary tumors from growing. Another benefit of our research could be the future development of “regenerative medicine” techniques. In other words, patients who have deficiencies in pituitary hormones as a result of pituitary tumors could be treated by replenishing the deficient cells using pituitary stem cells. The ultimate expectation is that they would be able to form healthy pituitary cells. With each pituitary tumor that we generously receive from our patients, we get closer to understanding how these tumors form and how we can treat them.