CCBIO Seminar – Randolph Watnick
Speaker: Randolph Watnick, Vascular Biology Program, Boston Children's Hospital, and Department of Surgery, Harvard Medical School, Boston, MA, USA. Title: "Identification of a novel paracrine acting stimulator of tumor growth and progression via modulation of Tsp-1 in the tumor microenvironment." The seminar will be held through a digital platform (Zoom Webinar), so you can attend even from the comfort of your own home.
Speaker: Randolph Watnick, Vascular Biology Program, Boston Children's Hospital, and Department of Surgery, Harvard Medical School, Boston, MA, USA
Randy is also one of CCBIO's international affiliated investigators.
Title: "Identification of a novel paracrine acting stimulator of tumor growth and progression via modulation of Tsp-1 in the tumor microenvironment"
Abstract: see below.
Place: digital event as webinar in Zoom. Access code as audience: https://uib.zoom.us/j/61605526770?pwd=bDlETkxWZUNrcWdFUEhNQ1RMdGtCUT09
If asked for a passcode, use this: ngDxN9d7
Time: March 25, 2021 at 14:30 (Norwegian time zone, Boston time is 09:30)
Chair: Lars A. Akslen
Open to all.
Bio: Randy Watnick received his PhD in biochemistry and biophysics from Columbia University in 1999, and was a postdoctoral fellow with Dr. Robert Weinberg, Whitehead Institute, Cambridge, MA, until 2003. Dr. Watnick is currently assistant professor at the Department of Surgery, Harvard Medical School and research associate in the Vascular Biology Program (VBP) at Boston Children’s Hospital.
Dr. Watnick’s expertise is in tumor stromal interactions, regulators of metastasis and gene regulation in epithelial and mesenchymal cells. His research group studies the regulation of angiogenesis, proliferation and motility in both epithelial cells and fibroblasts. The team has identified a novel suppressor of metastasis, prosaposin, which acts both locally and distally by stimulating the expression and activity of p53, which then stimulates the expression of Tsp-1. Significantly, prosaposin also inhibits both primary tumor growth and metastasis when administered in a systemic fashion, thus making it a potential therapeutic agent to stem the metastatic dissemination of human tumors. Dr. Watnick’s group has also developed a therapeutic peptide derived from prosaposin, which has been licensed to Vigeo Therapeutics and is currently in clinical trials in the United States.
Dr. Watnick has a longstanding collaboration with Lars A. Akslen on several projects, which among other has made important findings related to the role of Notch1 in breast cancer initiation and progression. Their collaboration on the tumor microenvironment has led to important observations related to CD36, CD47 and prosaposin expression in pancreatic cancer and their correlations to outcome and patient survival.
Abstract: In the earliest stages of tumor development, epithelial tumors (carcinomas) are physically confined to the area of the tissue in which they form. These nascent lesions (carcinomas in situ) are sequestered from the tissue parenchyma by the basement membrane. Within the tissue parenchyma lie a myriad of cell types comprised of fibroblasts, immune and inflammatory cells and endothelial cells. Upon invasion across the basement membrane and into the tissue parenchyma, tumors must manipulate the expression of pro- and anti-tumorigenic proteins such that pro-tumorigenic factors are produced in vast excess to anti-tumorigenic proteins. One such anti-tumorigenic protein is Thrombospondin-1 (Tsp-1). We have previously demonstrated that stimulation of Tsp-1 in the tumor microenvironment (TME) potently inhibits tumor growth and progression and in some cases induces tumor regression. Here, we identify a novel tumor-mediated mechanism to repress the expression of Tsp-1 in the TME via secretion of the serine protease PRSS2. We demonstrate that PRSS2 represses Tsp-1, not via its enzymatic activity, but by binding to the low-density lipoprotein receptor-related protein 1 (LRP1). These findings describe a novel activity for PRSS2 as well as novel ligand and activity for LRP1 and represent a potential therapeutic strategy to treat cancer by blocking the PRSS2-mediated repression of Tsp-1.