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

doi:10.1038/bjc.2017.140

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

Department of Clinical Medicine

19 Citations (Scopus)

76 Downloads (Pure)

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 language	English
Journal	British Journal of Cancer
Volume	117
Pages (from-to)	65-77
Number of pages	13
ISSN	0007-0920
DOIs	https://doi.org/10.1038/bjc.2017.140
Publication status	Published - 27 Jun 2017

Keywords

EMT
fibroblasts
HMGA2
pancreatic cancer
prognosis
stroma cells

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/bjc.2017.140Licence: CC BY-NC-SA

Stroma-regulated HMGA2 is an independent prognostic marker in PDAC and AACFinal published version, 3.19 MBLicence: CC BY-NC-SA

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Strell, C., Norberg, K. J., Mezheyeuski, A., Schnittert, J., Kuninty, P. R., Moro, C. F., Paulsson, J., Schultz, N. A., Calatayud, D., Löhr, J. M., Frings, O., Verbeke, C. S., Heuchel, R. L., Prakash, J., Johansen, J. S., & Östman, A. (2017). Stroma-regulated HMGA2 is an independent prognostic marker in PDAC and AAC. British Journal of Cancer, 117, 65-77. https://doi.org/10.1038/bjc.2017.140

Strell, C, Norberg, KJ, Mezheyeuski, A, Schnittert, J, Kuninty, PR, Moro, CF, Paulsson, J, Schultz, NA, Calatayud, D, Löhr, JM, Frings, O, Verbeke, CS, Heuchel, RL, Prakash, J, Johansen, JS & Östman, A 2017, 'Stroma-regulated HMGA2 is an independent prognostic marker in PDAC and AAC', British Journal of Cancer, vol. 117, pp. 65-77. https://doi.org/10.1038/bjc.2017.140

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title = "Stroma-regulated HMGA2 is an independent prognostic marker in PDAC and AAC",

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.",

keywords = "EMT, fibroblasts, HMGA2, pancreatic cancer, prognosis, stroma cells",

author = "Carina Strell and Norberg, {Karin Jessica} and Artur Mezheyeuski and Jonas Schnittert and Kuninty, {Praneeth R.} and Moro, {Carlos Fern{\'a}ndez} and Janna Paulsson and Schultz, {Nicolai Aagaard} and Dan Calatayud and L{\"o}hr, {Johannes Matthias} and Oliver Frings and Verbeke, {Caroline Sophie} and Heuchel, {Rainer Lothar} and Jai Prakash and Johansen, {Julia Sidenius} and Arne {\"O}stman",

year = "2017",

month = jun,

day = "27",

doi = "10.1038/bjc.2017.140",

language = "English",

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pages = "65--77",

journal = "The British journal of cancer. Supplement",

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T1 - Stroma-regulated HMGA2 is an independent prognostic marker in PDAC and AAC

AU - Strell, Carina

AU - Norberg, Karin Jessica

AU - Mezheyeuski, Artur

AU - Schnittert, Jonas

AU - Kuninty, Praneeth R.

AU - Moro, Carlos Fernández

AU - Paulsson, Janna

AU - Schultz, Nicolai Aagaard

AU - Calatayud, Dan

AU - Löhr, Johannes Matthias

AU - Frings, Oliver

AU - Verbeke, Caroline Sophie

AU - Heuchel, Rainer Lothar

AU - Prakash, Jai

AU - Johansen, Julia Sidenius

AU - Östman, Arne

PY - 2017/6/27

Y1 - 2017/6/27

N2 - 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.

AB - 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.

KW - EMT

KW - fibroblasts

KW - HMGA2

KW - pancreatic cancer

KW - prognosis

KW - stroma cells

U2 - 10.1038/bjc.2017.140

DO - 10.1038/bjc.2017.140

M3 - Journal article

C2 - 28524160

AN - SCOPUS:85021392828

SN - 0007-0920

VL - 117

SP - 65

EP - 77

JO - The British journal of cancer. Supplement

JF - The British journal of cancer. Supplement

ER -

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

Abstract

Keywords

UN SDGs

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