טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentBarbarov Yelena
SubjectThe Role of JDP2 Expression in the Host in Tumor Growth
and Metastasis
DepartmentDepartment of Medicine
Supervisors Professor Yuval Shaked
Professor Ami Aronheim
Full Thesis textFull thesis text - English Version


Abstract

The c-Jun Dimerization Protein 2, JDP2, is a basic leucine zipper protein member of the AP-1 family of transcription factors. It can bind TRE and CRE DNA elements. JDP2 typically suppresses gene transcription through multiple mechanisms and plays a dual role in multiple cellular processes including cell differentiation and proliferation depending on AP-1 function. Whereas the role of JDP2 expression within cancer cells is well studied, its role in stromal cells at the tumor microenvironment is largely unknown. Here we show that mice lacking JDP2 (JDP2-/-) display a reduced rate of metastasis in Lewis lung carcinoma (LLC) and Polyoma middle T-antigen (PyMT) breast carcinoma mouse models. The replacement of wild-type bone marrow derived cells (BMDCs) with JDP2-deficient BMDCs recapitulates the metastatic phenotype of JDP2-/- tumor-bearing mice.  In vitro, conditioned medium of wild-type BMDCs significantly potentiates the migration and invasion capacity of LLC cells as compared to that of JDP2-/- BMDCs. Furthermore, wild-type BMDCs secrete chemokine ligand 5(CCL5), a chemokine known to contribute to metastasis, to a greater extent than JDP2-/- BMDCs. The supplementation of CCL5 in JDP2-/- BMDC conditioned medium was sufficient to potentiate the invasion capacity of LLC. Overall, this study suggests that JDP2-expressing BMDCs within the tumor microenvironment contribute to metastasis spread.