Losartan slows pancreatic tumor progression and extends survival of SPARC-null mice by abrogating aberrant TGFβ activation.

PloS One
Shanna ArnoldRolf A Brekken

Abstract

Pancreatic adenocarcinoma, a desmoplastic disease, is the fourth leading cause of cancer-related death in the Western world due, in large part, to locally invasive primary tumor growth and ensuing metastasis. SPARC is a matricellular protein that governs extracellular matrix (ECM) deposition and maturation during tissue remodeling, particularly, during wound healing and tumorigenesis. In the present study, we sought to determine the mechanism by which lack of host SPARC alters the tumor microenvironment and enhances invasion and metastasis of an orthotopic model of pancreatic cancer. We identified that levels of active TGFβ1 were increased significantly in tumors grown in SPARC-null mice. TGFβ1 contributes to many aspects of tumor development including metastasis, endothelial cell permeability, inflammation and fibrosis, all of which are altered in the absence of stromal-derived SPARC. Given these results, we performed a survival study to assess the contribution of increased TGFβ1 activity to tumor progression in SPARC-null mice using losartan, an angiotensin II type 1 receptor antagonist that diminishes TGFβ1 expression and activation in vivo. Tumors grown in SPARC-null mice progressed more quickly than those grown in wild-typ...Continue Reading

References

Feb 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·E W RainesE H Sage
Jul 1, 1995·American Journal of Respiratory Cell and Molecular Biology·A SantanaB C Marshall
Apr 1, 1995·Developmental Dynamics : an Official Publication of the American Association of Anatomists·R HallmannE C Butcher
Oct 24, 1994·FEBS Letters·H HausserH Kresse
Oct 1, 1993·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·M J ReedE H Sage
Jan 15, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Jose A NadalA Guillermo Scicli
Mar 6, 2002·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Rajiv AgarwalKumar Sharma
Jun 20, 2002·Methods in Cell Biology·Paul Bornstein
Oct 22, 2002·FEBS Letters·Ellen Tufvesson, Gunilla Westergren-Thorsson
Feb 18, 2003·The Journal of Clinical Investigation·Rolf A BrekkenE Helene Sage
Mar 23, 2004·Journal of Cellular Biochemistry·Aleksandar FranckiE Helene Sage
Jun 24, 2004·Journal of Cellular Biochemistry·Paul E Framson, E Helene Sage
Nov 29, 2005·Biochemical and Biophysical Research Communications·Yong ZhouJoanne E Murphy-Ullrich
Jun 26, 2007·World Journal of Gastroenterology : WJG·Franck Verrecchia, Alain Mauviel
Jul 13, 2007·Gut·Paula GhanehJohn P Neoptolemos
Aug 31, 2007·Nature Clinical Practice. Oncology·Christoph W MichalskiMarkus W Büchler
Oct 6, 2007·Advanced Drug Delivery Reviews·Lauren MacriRichard A F Clark
Jun 11, 2008·Cancer Metastasis Reviews·Osvaldo L PodhajcerAndrea S Llera
Jun 20, 2008·Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus·T OsakiM Ikeguchi
Jun 27, 2008·The New England Journal of Medicine·Benjamin S BrookeHarry C Dietz
Jan 21, 2009·Cell Research·Jian XuRik Derynck
Apr 4, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Suzanne Ostrand-Rosenberg, Pratima Sinha
Jun 2, 2009·Frontiers in Bioscience (Landmark Edition)·Evangelia Pardali, Peter ten Dijke
Jun 13, 2009·Current Pharmaceutical Design·Marc Beyer, Joachim L Schultze

❮ Previous
Next ❯

Citations

Feb 4, 2014·Progrès en urologie : journal de l'Association française d'urologie et de la Société française d'urologie·G VerhoestC Vigneau
Mar 29, 2014·Carcinogenesis·Ganji Purnachandra NagarajuSajani S Lakka
Jan 17, 2013·The Journal of Clinical Investigation·Neveen SaidDan Theodorescu
May 22, 2013·Cancer Metastasis Reviews·Cindy NeuzilletEric Raymond
Jan 22, 2013·Néphrologie & thérapeutique·Thibault Dolley-HitzeCécile Vigneau
Apr 14, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Mikhail O DurymanovAlexander S Sobolev
Jul 11, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Chandraiah GoduguMandip Singh
Apr 15, 2014·Hernia : the Journal of Hernias and Abdominal Wall Surgery·C N CrissM J Rosen
Mar 18, 2017·Journal of the Renin-angiotensin-aldosterone System : JRAAS·Zhang YueXue Feng-Xia
Dec 24, 2016·Cancer Biomarkers : Section a of Disease Markers·Neslihan KurtulCelalettin Eroglu
Jun 13, 2017·Journal of Surgical Oncology·Laleh G MelstromDon J Diamond
Oct 6, 2017·Science Translational Medicine·Matthias Pinter, Rakesh K Jain
Mar 22, 2019·The Cancer Journal·Matthias IlmerBernhard W Renz
Apr 12, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Daniel P ReganSteven W Dow
Feb 16, 2020·British Journal of Pharmacology·Krishna SriramPaul A Insel
Oct 31, 2014·World Journal of Gastroenterology : WJG·Ferda Kaleağasıoğlu, Martin R Berger
Aug 12, 2020·Journal of Cellular Physiology·Ji-Ming BaoWan-Long Tan
Dec 18, 2015·Cancer Research·Venugopal R MittapalliLeena Bruckner-Tuderman
Jan 21, 2021·Cancers·Pia GamradtAna Hennino
Mar 3, 2020·Cancer Letters·Amanda MunasingheNatasha J Hill
Mar 17, 2020·Pharmacology & Therapeutics·Marcos V PeriniAshwini L Chand
May 25, 2021·World Journal of Gastroenterology : WJG·Faran PolaniKian-Huat Lim
May 2, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Elham AhmadianMohammad Ali Eghbal

❮ Previous
Next ❯

Methods Mentioned

BETA
ELISA
PCR
fluorescence microscopy
enzyme-linked immunosorbent assay
protein assay

Software Mentioned

GraphPad
RT 2 Profiler⢠PCR Array
NIS Elements AR
GraphPad Prism
Act1

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Basement Membranes

Basement membranes are thin, specialized extracellular matrices surrounding most tissues in all metazoans. Here is the latest research on basement membranes.

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.

Cadherins and Catenins

Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.