Targeting pancreatic ductal adenocarcinoma acidic microenvironment

Sci Rep. 2014 Mar 19;4:4410. doi: 10.1038/srep04410.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA, accounting for ~40,000 deaths annually. The dismal prognosis for PDAC is largely due to its late diagnosis. Currently, the most sensitive diagnosis of PDAC requires invasive procedures, such as endoscopic ultrasonography, which has inherent risks and accuracy that is highly operator dependent. Here we took advantage of a general characteristic of solid tumors, the acidic microenvironment that is generated as a by-product of metabolism, to develop a novel approach of using pH (Low) Insertion Peptides (pHLIPs) for imaging of PDAC. We show that fluorescently labeled pHLIPs can localize and specifically detect PDAC in human xenografts as well as PDAC and PanIN lesions in genetically engineered mouse models. This novel approach may improve detection, differential diagnosis and staging of PDAC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carcinoma, Pancreatic Ductal / diagnosis*
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / secondary
  • Cell Line, Tumor
  • Diagnostic Imaging / methods*
  • Disease Models, Animal
  • Humans
  • Hydrogen-Ion Concentration
  • Mice
  • Mice, Nude
  • Molecular Sequence Data
  • Neoplasm Transplantation
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Peptides* / chemical synthesis
  • Peptides* / metabolism
  • Peritoneal Neoplasms / diagnosis*
  • Peritoneal Neoplasms / metabolism
  • Peritoneal Neoplasms / secondary
  • Prognosis
  • Tumor Microenvironment

Substances

  • Peptides