Next Article in Journal
Cytokine and Adipokine Levels in Patients with Premalignant Oral Lesions or in Patients with Oral Cancer Who Did or Did Not Receive 1α,25-Dihydroxyvitamin D3 Treatment upon Cancer Diagnosis
Next Article in Special Issue
Targeting NK-1 Receptors to Prevent and Treat Pancreatic Cancer: a New Therapeutic Approach
Previous Article in Journal
Oncogenic BRAF(V600E) Induces Clastogenesis and UVB Hypersensitivity
Previous Article in Special Issue
Pathologic Cellular Events in Smoking-Related Pancreatitis
Article Menu

Export Article

Open AccessReview
Cancers 2015, 7(2), 1091-1108; doi:10.3390/cancers7020826

Role of Parathyroid Hormone-Related Protein Signaling in Chronic Pancreatitis

Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Hildegard M. Schuller
Received: 27 April 2015 / Revised: 5 June 2015 / Accepted: 9 June 2015 / Published: 18 June 2015
View Full-Text   |   Download PDF [368 KB, uploaded 18 June 2015]   |  

Abstract

Chronic pancreatitis (CP), a progressive inflammatory disease where acini are destroyed and replaced by fibrous tissue, increases the risk for pancreatic cancer. Risk factors include alcohol, smoking, and obesity. The effects of these risk factors are exacerbated in patients with mutations in genes that predispose to CP. The different environmental and genetic factors produce the same clinical phenotype; once CP develops, disease course is the same regardless of etiology. Critical questions still need to be answered to understand what modifies predisposition to develop CP in persons exposed to risk factors. We postulate that risk factors modulate endogenous pathways, with parathyroid hormone-related protein (PTHrP) signaling being one such pathway. In support, PTHrP levels are elevated in mice treated with alcohol, and in mouse models of cerulein- and pancreatic duct ligation-induced CP. Disrupting the Pthrp gene in acinar cells exerts protective effects (decreased edema, histological damage, amylase and cytokine release, and fibrosis) in these CP models. PTHrP levels are elevated in human CP. Currently, CP care lacks specific pharmacological interventions. Targeting PTHrP signaling may present a novel therapeutic strategy that inhibits pancreatic inflammation and fibrosis, especially since the risk of developing pancreatic cancer is strongly associated with duration of chronic inflammation. View Full-Text
Keywords: parathyroid hormone-related protein; alcohol; acinar cells; stellate cells; cytokines; extracellular matrix parathyroid hormone-related protein; alcohol; acinar cells; stellate cells; cytokines; extracellular matrix
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Falzon, M.; Bhatia, V. Role of Parathyroid Hormone-Related Protein Signaling in Chronic Pancreatitis. Cancers 2015, 7, 1091-1108.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top