Stroma-regulated HMGA2 is an independent prognostic marker in PDAC and AAC

Carina Strell*, Karin Jessica Norberg, Artur Mezheyeuski, Jonas Schnittert, Praneeth R. Kuninty, Carlos Fernández Moro, Janna Paulsson, Nicolai Aagaard Schultz, Dan Calatayud, Johannes Matthias Löhr, Oliver Frings, Caroline Sophie Verbeke, Rainer Lothar Heuchel, Jai Prakash, Julia Sidenius Johansen, Arne Östman

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Background: The HMGA2 protein has experimentally been linked to EMT and cancer stemness. Recent studies imply that tumour-stroma interactions regulate these features and thereby contribute to tumour aggressiveness.

Methods: We analysed 253 cases of pancreatic ductal adenocarcinoma (PDAC) and 155 cases of ampullary adenocarcinoma (AAC) for HMGA2 expression by IHC. The data were correlated with stroma abundance and supplemented by experimental studies.

Results: HMGA2 acts as an independent prognostic marker associated with a significantly shorter overall survival in both tumour types. Overall, HMGA2-positivity was more frequent in patients with PDAC than with AAC. The HMGA2 status in tumour cells significantly correlated with the abundance of PDGFRβ-defined stroma cells. In vivo co-injection of Panc-1 cancer cells with pancreatic stellate cells increased tumour growth in a manner associated with increased HMGA2 expression. Furthermore, in vitro treatment of Panc-1 with conditioned media from PDGF-BB-activated stellate cells increased their ability to form tumour spheroids.

Conclusions: This study identifies HMGA2 expression in tumour cells as an independent prognostic marker in PDAC and AAC. Correlative data analysis gives novel tissue-based evidence for a heterotypic cross-talk with stroma cells as a possible mechanism for HMGA2 induction, which is further supported by experimental models.

Original languageEnglish
Pages (from-to)65-77
Number of pages13
JournalBritish journal of cancer
Volume117
Issue number1
DOIs
Publication statusPublished - 27 Jun 2017

Keywords

  • EMT
  • fibroblasts
  • HMGA2
  • pancreatic cancer
  • prognosis
  • stroma cells

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