Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2021
Erindi/veggspjald / Talk/poster E70
Höfundar / Authors: Clara Valls Ferré (1), Guðrún Valdimarsdóttir (1), Kristian Pietras (2), Helga Þráinsdóttir (1)
Starfsvettvangur / Affiliations: 1. University of Iceland, 2. Lund University
Kynnir / Presenter: Clara Valls Ferré
The most common cancer in women worldwide is breast cancer and the diagnosis of its metastasis worsens significantly the patient’s prognosis. The molecular relation between disseminated cancer cells and their microenvironment is poorly described. Recent studies suggest that disseminated tumor cells residing close to the endothelium stay dormant, but, upon activation cues in the microenvironment, these cells can exit the dormancy state, starting proliferating and spreading metastatically, as angiogenesis is enhanced. Thrombospondin-1 (TSP-1) is an extracellular secreted glycoprotein and an angiogenesis inhibitor expressed in resting endothelial cells. TGFβ has a two-sided role acting through ALK receptors, suppressing and promoting angiogenesis. We hypothesize that endothelial derived TSP-1 suppresses metastatic growth but, by tumor microenvironment and angiogenesis activation, the TSP-1 is relieved and metastasis developed. In vitro studies on cancer cells and mouse models were used to deepen in the basis of the TGFβ signalling pathway and the relation between the tumor cells and their microenvironment. Those studies showed that TGFβ induces TSP-1 expression in endothelial cells and that TSP-1 seems to regulate the metastasis inhibition in quiescent endothelium. We envision a combined target molecular therapy to inhibit angiogenesis. This insight will have huge impact on the development of therapeutic tools to prevent metastasis in breast cancer patients.