Silvia E. Hajos
Accepted Abstracts: J Cancer Sci Ther
Tumor microenvironment influences tumor growth, therefore extracellular matrix components (EMC) are important players in such process. Hyaluronan (HA) is a major component of the ECM, implicated in tumor survival and progression upon interaction with its receptors CD44 and RHAMM. Their involvement in growth of different kind of solid tumors have been reported. However, little is known about the role of HA in hematological malignancies. In this lecture, I will describe the results obtained in our laboratory on the presence and function of such ECM components using two different models: a) sensitive and resistant human leukemic cell lines, b) tissue from patients with gestational trophoblastic disease (GTD). Up to now, we demonstrated that HA induced cell proliferation on K562 vincristine (VCR) sensitive and Kv562 VCR resistant leukemic human cell lines. This effect was mediated by CD44 and activation of both PI3K/Akt and MEK/ERK pathways on K562, whereas on Kv562 it was mediated by RHAMM and PI3K/Akt activation. HA synthesis inhibition decreased cell proliferation and sensitized Kv562 to the effect of VCR, in both cases with senescence induction. Oligosaccharides obtained from HA (oHA) inhibited the effect sensitizing Kv562 cells to VCR by Pgp inhibition. GTD constitutes a group of disorders that arises from the placental trophoblast including hydatiform mole, choriocarcinoma (CC) and placental-site-trophoblastic-tumor, representing malignant fetal allografts in maternal tissues. We analyzed the presence and distribution of HA, CD44 and RHAMM in tissues collected from the Pathology Service of Hospital Durand, Bs As, Argentina. We found different subcellular distribution of RHAMM in GTD tissues while HA and CD44 were related to the stroma only in CC, suggesting that such molecules are involved in the pathogenesis of GTD. We are working to elucidate their involvement in migration, invasion and metastasis processes as well as in immune response modulation.
Silvia E. Hajos has being investigating the role of CD44 and hyaluronan on tumor growth for the last 14 years. During her career, she published 100 peer-reviewed reports and presented almost 210 communications to different Immunology and Cancer meetings. She was also director of numerous Ph.D. theses at the University of Buenos Aires (UBA). Actually, she is a consultant Professor of Immunology at the Faculty of Pharmacy and Biochemistry, UBA, and is also a member of the National Research Council (CONICET) of her country. She has served on various review committees, including evaluation at Union for International Cancer Control.