Paracrine and cell autonomous signalling in pancreatic cancer progression and metastasis

EBioMedicine. 2020 Mar;53:102662. doi: 10.1016/j.ebiom.2020.102662. Epub 2020 Mar 2.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) shows remarkable propensity to metastasize. This predilection to escape from the primary tumor is driven by paracrine and autocrine mechanisms that guide cancer cells through a multi-step process concluding with colonization in distant tissues. Although cell-intrinsic features support the metastatic ability of cancer cells, permissive microenvironments within the primary organ and at sites of distant metastasis may be rate-limiting. Identification of cancer cell-extrinsic factors that regulate formation of these environments lend new therapeutic targets for intervening on the metastatic cascade. In addition, the bipolar, yet fundamental, role of the immune system in the metastatic process presents therapeutic opportunities. Herein, we review the current knowledge of the metastatic cascade in PDAC, and propose that genomically stable determinants of metastasis (e.g. the pro-metastatic niche and immune system) are actionable targets for preventing, containing, and treating metastasis in PDAC.

Keywords: Cancer; Clinical trials; Immune evasion; Immunosurveillance; Immunotherapy; Inflammation; Macrophages; Metastasis; Neutrophils; Pancreatic ductal adenocarcinoma; T cells; Therapeutic resistance; Treatment paradigms; Tumor microenvironment; Vaccines.

Publication types

  • Review

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Animals
  • Humans
  • Immune Evasion
  • Neoplasm Metastasis
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Paracrine Communication*
  • Stem Cell Niche
  • Wnt Signaling Pathway