טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentAbed Al Wahad Ali
SubjectThe Role of Pregnancy in Promoting Lymphoma Growth and
Dissemination
DepartmentDepartment of Medicine
Supervisors Dr. Netanel Horowitz
Dr. Tamar Katz
Full Thesis textFull thesis text - English Version


Abstract

Lymphoma is the most common hematological cancer reported during pregnancy. Recent data suggest that unlike lymphoma occurring outside of pregnancy, pregnancy-associated lymphoma is characterized by an excessive involvement of reproductive organs, advanced disease stage at diagnosis and an aggressive course, potentially leading to a high death rate of mothers. Several mechanisms may be responsible for lymphoma progression during pregnancy. High levels of sex hormones could diminish immune activity, while the expression of hormone receptors on lymphoma cells may facilitate migration of cancer cells to reproductive organs and affect disease aggressiveness. The microenvironment, protecting tumor cells from immune surveillance and chemotherapy, may promote growth of lymphoma cell. Sex hormones may alter the function of several cellular components composing tumor microenvironment, thereby, directly or indirectly contributing to homing, survival and growth of tumor cells. We hypothesize that pregnancy induced hormonal environment is an important mediator in the interaction between lymphoma cells and cells surrounding them. This process may be a potent contributor to the growth and progress of lymphoma developing during pregnancy. Our results have demonstrated that in in-vivo model; pregnant mice showed accelerated tumor growth following lymphoma inoculation compared to non-pregnant mice. In In-vitro experiments, several lymphoma cell lines, as well as lymph node stromal cell line exhibit sex hormone receptors which are induced by pregnancy. Treatment of lymphoma cells with estrogen resulted in an increase in cell proliferation that was seen in two of three examined lymphoma cell lines and was mediated by estrogen receptor α and β. Estrogen also induced the expression of VEGFs in lymphoma and lymph node stromal cells and their receptor in lymphoma cells. MMPs expression was also increased in lymphoma and lymph node stromal cells in response to E2 treatment. Progesterone almost had no effect on lymphoma cells proliferation, viability and migration when administered alone. These findings support our hypothesis that pregnancy facilitates lymphoma growth and aggressiveness, suggesting that estrogen partially responsible for lymphoma progression by affecting lymphoma cells and cells in their surrounding that take an active role in lymphoma growth.