1. Stroma-regulated HMGA2 is an independent prognostic marker in PDAC and AAC.
- Author
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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, and Östman A
- Subjects
- Adenocarcinoma pathology, Aged, Ampulla of Vater, Animals, Carcinoma, Pancreatic Ductal pathology, Cell Line, Tumor, Common Bile Duct Neoplasms pathology, Female, Humans, Immunohistochemistry, Male, Mice, Mice, SCID, Middle Aged, Multivariate Analysis, Neoplasm Staging, Neoplasm Transplantation, Pancreatic Neoplasms pathology, Pancreatic Stellate Cells metabolism, Prognosis, Receptor, Platelet-Derived Growth Factor beta metabolism, Reverse Transcriptase Polymerase Chain Reaction, Stromal Cells metabolism, Survival Rate, Adenocarcinoma metabolism, Carcinoma, Pancreatic Ductal metabolism, Common Bile Duct Neoplasms metabolism, HMGA2 Protein metabolism, Pancreatic Neoplasms metabolism
- 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.
- Published
- 2017
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