Leukemia Cell Trafficking and Microenvironment
Chronic lymphocytic leukemia (CLL) is an incurable malignancy of B lymphocytes accumulating in the blood, bone marrow and secondary lymphoid organs. The proliferation and survival of CLL cells requires their stimulation by the lymphoid microenvironment. Therein, a complex interplay of malignant and accessory cells, the extracellular matrix, and soluble factors determines the balance between proliferating and resting tumor cells. Molecules regulating CLL cell localization inside lymphoid organs are thus of high pathophysiological interest.
We study adhesion molecules such as integrins and CD44 and chemokine receptors such as CXCR4 that mediate lymphocyte/leukocyte extravasation from the blood vessel as well as interstitial motility within the microenvironment to localize at the appropriate site for proliferation and survival.
We use a combination of immunohistochemical, video-microscopical and cell biological approaches as well as mouse models to dissect the contributions of these molecules including their interplay, their cytoskeletal connections and downstream signals. Therapeutic interference with these interactions may release the tumor cells from their protective niches, prevent their proliferation, and eventually provide strong synergism with conventional therapies.
Tanja Hartman, PhD
Assoc. Prof. for Molecular Cancer Research
Cancer cell - microenvironment interactions
Characterization of CLL cell-microenvironment interactions with respect to adhesion molecules (integrins, CD44) and chemokine receptors is one of our group's main aims. These molecules mediate lymphocyte/leukocyte extravasation from the blood vessel as well as interstitial motility within the microenvironment to localize at the appropriate site for proliferation and survival. Therapeutical interference with (malignant) cell localization may suppress minimal residual disease after chemotherapy and the development of chemoresistance.