The small heat shock protein αA-crystallin negatively regulates pancreatic tumorigenesis

Oncotarget. 2016 Oct 4;7(40):65808-65824. doi: 10.18632/oncotarget.11668.

Abstract

Our recent study has shown that αA-crystallin appears to act as a tumor suppressor in pancreas. Here, we analyzed expression patterns of αA-crystallin in the pancreatic tumor tissue and the neighbor normal tissue from 74 pancreatic cancer patients and also pancreatic cancer cell lines. Immunocytochemistry revealed that αA-crystallin was highly expressed in the normal tissue from 56 patients, but barely detectable in the pancreatic tumor tissue. Moreover, a low level of αA-crystallin predicts poor prognosis for patients with pancreatic duct adenocarcinoma (PDAC). In the 12 pancreatic cell lines analyzed, except for Capan-1 and Miapaca-2 where the level of αA-crystallin was about 80% and 65% of that in the control cell line, HPNE, the remaining pancreatic cancer cells have much lower αA-crystallin levels. Overexpression of αA-crystallin in MiaPaca-1 cells lacking endogenous αA-crystallin significantly decreased its tumorigenicity ability as shown in the colony formation and wound healing assays. In contrast, knockdown of αA-crystallin in the Capan-1 cells significantly increased its tumorigenicity ability as demonstrated in the above assays. Together, our results further demonstrate that αA-crystallin negatively regulates pancreatic tumorigenesis and appears to be a prognosis biomarker for PDAC.

Keywords: cancer therapy; pancreatic cancer; small heat shock protein; tumor suppression; αA.

MeSH terms

  • Aged
  • Apoptosis
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / pathology*
  • Carcinoma, Pancreatic Ductal / surgery
  • Cell Proliferation
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Neoplasms / surgery
  • Prognosis
  • Survival Rate
  • Tumor Cells, Cultured
  • alpha-Crystallin A Chain / metabolism*

Substances

  • Biomarkers, Tumor
  • alpha-Crystallin A Chain