British journal of cancer · 2017
Stroma-regulated HMGA2 is an independent prognostic marker in PDAC and AAC.
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Strell Carina, Norberg Karin Jessica, Mezheyeuski Artur, Schnittert Jonas, Kuninty Praneeth R, Moro Carlos Fernández, Paulsson Janna, Schultz Nicolai Aagaard, Calatayud Dan, Löhr Johannes Matthias, Frings Oliver, Verbeke Caroline Sophie, Heuchel Rainer Lothar, Prakash Jai, Johansen Julia Sidenius, Östman Arne
Аннотация
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.
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.
Предметные рубрики MeSH
AdenocarcinomaAgedAmpulla of VaterAnimalsCarcinoma, Pancreatic DuctalCell Line, TumorCommon Bile Duct NeoplasmsFemaleHMGA2 ProteinHumansImmunohistochemistryMaleMiceMice, SCIDMiddle AgedMultivariate AnalysisNeoplasm StagingNeoplasm TransplantationPancreatic NeoplasmsPancreatic Stellate CellsPrognosisReceptor, Platelet-Derived Growth Factor betaReverse Transcriptase Polymerase Chain ReactionStromal CellsSurvival Rate