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Br J Cancer. 2017 Jun 27;117(1):65-77. doi: 10.1038/bjc.2017.140. Epub 2017 May 18.

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

Author information

1
Department of Oncology-Pathology, Cancer Center Karolinska (CCK), Karolinska Institutet, Stockholm 17176, Sweden.
2
Department of Clinical Intervention and Technology (CLINTEC), Center for Digestive Diseases, Karolinska University Hospital and Division of Surgery, Karolinska Institutet, Stockholm 14186, Sweden.
3
Department of Biomaterials Science and Technology, Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Zuidhorst building, ZH254, Enschede 7500AE, The Netherlands.
4
Department of Laboratory Medicine (LabMed) Division of Pathology, Karolinska Institutet, Stockholm 14186, Sweden.
5
Department of Clinical Pathology/Cytology, Karolinska University Hospital, Stockholm 14186, Sweden.
6
Department of Surgical Gastroenterology and Transplantation, Rigshospitalet, Copenhagen University Hospital, Copenhagen 2100, Denmark.
7
Department of Oncology-Pathology, Science for Life Laboratory, Karolinska Institutet, Stockholm 17176, Sweden.
8
Institute of Clinical Medicine, University of Oslo, Postbox 1171 Blindern, Oslo 0318, Norway.
9
Department of Pathology, Oslo University Hospital, Rikshospitalet, Postbox 4956 Nydalen, Oslo 0424, Norway.
10
Department of Oncology and Medicine, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev 2730, Denmark.

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.

PMID:
28524160
PMCID:
PMC5520204
DOI:
10.1038/bjc.2017.140
[Indexed for MEDLINE]
Free PMC Article

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