CCBIO-seminar – Juan Rodríguez Vita

(Engelsk tekst videre siden seminarene er internasjonale og undervisningsspråket på seminarene er engelsk.)

Speaker: Juan Rodríguez Vita, Centro de Investigacíon Príncipe Felipe, Valencia, Spain.
Title: Hyaluronic acid is a master regulator of tumor stroma
Topic: Tumor-stroma communication
Host: Line Bjørge
Where: Auditorium 4, BB-building
When: August 31, 2023 at 14.30-15.30

No registration necessary. 

Dr. Juan Rodríguez Vita obtained his PhD at the FJD in Madrid (Spain), and after postdoctoral periods at the CIML in Marseille (France) and the IDIBAPS in Barcelona (Barcelona), he is currently a Project leader in the Vascular Signaling and Cancer Division at the DKFZ in Heidelberg (Germany). He started his own group at the CIPF in Valencia (Spain) on September 2021. His research focuses on deciphering the communication signals between tumor cells and stroma. 

Abstract:  Tumor cells use signals to communicate and educate the tumor stroma. These signals are often present in the extracellular matrix (ECM). I will show you how tumor cells take advantage of one of the components of this ECM, hyaluronic acid (HA), to modify their stroma in order to generate a more immunosuppressive environment and increase their metastatic potential. HA can be synthesized as low molecular weight-HA (LMW-HA) or high molecular weight-HA (HMW-HA). Firstly, I will describe how HMW-HA produced by ovarian cancer cells, when recognized by macrophages, depletes membrane cholesterol from their plasma membranes. Cholesterol depletion alters IL-4 signaling and amplifies its responses. Secondly, I will show how tumor cells precondition monocytes even before they arrive into the tumor microenvironment, by regulating HA receptors. Notch1 receptors (N1ICD) are frequently activated in Endothelial cells (ECs) within human tumors. Using VECadherin-CreERT2 transgenic mice to induce gene recombination exclusively in adult ECs, we explored the role of Notch signaling in ECs in vivo. RbpjiΔEC (VECad-rERT2xRbpjflox) mice inhibit the canonical Notch signaling upon tamoxifen administration. Thanks to these mice, we were able to demonstrate that Notch signaling in endothelial cells leads to a CXCL2 dependent regulation of CD44 (and HA receptor) in monocytes, which facilitates tumor-associated macrophages education by tumor cells. Finally, I will explain how all this led us to study the role of HA in Pancreatic ductal adenocarcinoma (PDAC) where ECM can make up to 90 % of the desmoplastic tumor mass and HA is one if its main components. We found that Hyaluronan and proteoglycan link protein 1 (HAPLN1), which crosslinks HA with proteoglycans, is an important regulator of HA actions. We found that HAPLN1 induces a Hyperplastic phenotype in tumor cells, which promotes an immune-modulatory microenvironment that favors disease progression in vivo.

All interested researchers, students and others are welcome!