Konference: 2012 8. Sympozium a workshop molekulární patologie a histo-cyto-chemie
Kategorie: Genitourinární nádory; Nádorová biologie/imunologie/genetika a buněčná terapie
Téma: Keynote lectures of invited speakers III.
Číslo abstraktu: 008
Autoři: Mgr. Karel Souček, Ph.D.; Eva Slavíčková; Mgr. Eva Slabáková, Ph.D.; Mgr. Zuzana Pernicová; RNDr. Petr Vaňhara, Ph.D.; Doc. MvDr. Aleš Hampl, CSc.; Mgr. Jiří Kohoutek, Ph.D.; prof. RNDr. Alois Kozubík, CSc.
Cancer is not a single cell disease and thus the study of processes modulating tumor microenvironment, especially relation between cancer cells and immune system, has important clinical potential. Prostate cancer is a frequently diagnosed malignancy and the leading cause of cancer-related death in Western countries. New findings leading to better knowledge of how it is possible to modulate particular cell populations can suggest novel strategies for cancer prevention and therapy.
Deregulation of expression and function of cytokines belonging to Transforming Growth Factor – β (TGF-β) family is often associated with cancer progression. This family therefore represents great candidates for drug targeting. However there are still several cytokines from TGF-β family which could play role in cancer progression where their detailed function is still unclear. Such a cytokine is Growth/Differentiation Factor – 15 (GDF-15, MIC-1, NAG-1, PTGF) – a divergent member of TGF-β family. GDF- 15 is generally considered to be part of the cell’s antitumorigenic actions, mostly because of the fact that its expression is crucial for chemopreventive effects of various compounds. On the other hand its higher expression has been often reported during cancer progression. Our study published recently unveil new role of GDF-15 in modulation of osteoclast differentiation and possibly in therapy of bone metastases. Moreover, GDF-15 is as an abundant cytokine in seminal plasma with immunosuppressive properties. Here we showed that ectopic overexpression of mouse GDF- 15 in TRAMP-C1 cells sustained growth of solid tumors in vivo. However tumor incidence and size were significantly decreased when tumors were grafted in GDF-15-/- mice. Our data suggest that GDF-15 expressed in both cancer and normal cells has capacity to modulate cancer progression.
This work was supported by grants IGA MZD 9600–4/2008 and 13573/2012 and by project FNUSA-ICRC (no. CZ.1.05/1.1.00/02.0123) from the European Regional Development Fund.
Datum přednesení příspěvku: 27. 4. 2012
