PAPP-A and cancer

J Mol Endocrinol. 2018 Jul;61(1):T1-T10. doi: 10.1530/JME-17-0236.

Abstract

The zinc metalloproteinase, PAPP-A, enhances local insulin-like growth factor (IGF) action through cleavage of inhibitory IGF-binding proteins, thereby increasing IGF available for IGF receptor-mediated cell proliferation, migration and survival. In many tumors, enhanced IGF receptor signaling is associated with tumor growth, invasion and metastasis. We will first discuss PAPP-A structure and function, and post-translational inhibitors of PAPP-A expression or proteolytic activity. We will then review the evidence supporting an important role for PAPP-A in many cancers, including breast, ovarian and lung cancer, and Ewing sarcoma.

Keywords: Ewing sarcoma; breast cancer; insulin-like growth factor; lung cancer; melanoma; mesothelioma; ovarian cancer; pregnancy-associated plasma protein-A; stanniocalcin.

Publication types

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

MeSH terms

  • Animals
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Female
  • Glycoproteins / metabolism
  • Humans
  • Insulin-Like Growth Factor I / metabolism
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mesothelioma / metabolism
  • Mesothelioma / pathology
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Pregnancy-Associated Plasma Protein-A / genetics
  • Pregnancy-Associated Plasma Protein-A / metabolism*
  • Sarcoma, Ewing / metabolism
  • Sarcoma, Ewing / pathology

Substances

  • Glycoproteins
  • Insulin-Like Growth Factor I
  • teleocalcin
  • Pregnancy-Associated Plasma Protein-A