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000275610 1001_ $$0P:(DE-He78)b27922c32bcdf07ca4d5f13ecdcfd100$$aWiedmann, Lena$$b0$$eFirst author$$udkfz
000275610 245__ $$aHAPLN1 potentiates peritoneal metastasis in pancreatic cancer.
000275610 260__ $$a[London]$$bNature Publishing Group UK$$c2023
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000275610 520__ $$aPancreatic ductal adenocarcinoma (PDAC) frequently metastasizes into the peritoneum, which contributes to poor prognosis. Metastatic spreading is promoted by cancer cell plasticity, yet its regulation by the microenvironment is incompletely understood. Here, we show that the presence of hyaluronan and proteoglycan link protein-1 (HAPLN1) in the extracellular matrix enhances tumor cell plasticity and PDAC metastasis. Bioinformatic analysis showed that HAPLN1 expression is enriched in the basal PDAC subtype and associated with worse overall patient survival. In a mouse model for peritoneal carcinomatosis, HAPLN1-induced immunomodulation favors a more permissive microenvironment, which accelerates the peritoneal spread of tumor cells. Mechanistically, HAPLN1, via upregulation of tumor necrosis factor receptor 2 (TNFR2), promotes TNF-mediated upregulation of Hyaluronan (HA) production, facilitating EMT, stemness, invasion and immunomodulation. Extracellular HAPLN1 modifies cancer cells and fibroblasts, rendering them more immunomodulatory. As such, we identify HAPLN1 as a prognostic marker and as a driver for peritoneal metastasis in PDAC.
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000275610 7001_ $$0P:(DE-He78)95d56cbcb8b1bb5783526d136049e3df$$aDe Angelis Rigotti, Francesca$$b1$$eFirst author
000275610 7001_ $$0P:(DE-HGF)0$$aVaquero-Siguero, Nuria$$b2
000275610 7001_ $$0P:(DE-He78)b3e23abb6bede16f11543cc21ae0feeb$$aDonato, Elisa$$b3$$udkfz
000275610 7001_ $$00000-0002-0690-9878$$aEspinet, Elisa$$b4
000275610 7001_ $$0P:(DE-He78)68d90eb013f51c689f9ebea83a920858$$aMoll, Iris$$b5$$udkfz
000275610 7001_ $$00000-0002-5761-632X$$aAlsina-Sanchis, Elisenda$$b6
000275610 7001_ $$00000-0003-1038-1030$$aBohnenberger, Hanibal$$b7
000275610 7001_ $$00000-0003-3034-5109$$aFernandez-Florido, Elena$$b8
000275610 7001_ $$0P:(DE-He78)3d2b0a3563ccf6bc6ee65cf2976efe5f$$aMülfarth, Ronja$$b9
000275610 7001_ $$0P:(DE-He78)db0b2f396de01b200ce18462ab29fdbc$$aVacca, Margherita$$b10
000275610 7001_ $$0P:(DE-HGF)0$$aGerwing, Jennifer$$b11
000275610 7001_ $$aConradi, Lena-Christin$$b12
000275610 7001_ $$aStröbel, Philipp$$b13
000275610 7001_ $$0P:(DE-He78)732f4fbcddb0042251aa759a2e74d3b2$$aTrumpp, Andreas$$b14$$udkfz
000275610 7001_ $$aMogler, Carolin$$b15
000275610 7001_ $$0P:(DE-He78)039283a5d51058ec79156d0ef67132da$$aFischer, Andreas$$b16$$udkfz
000275610 7001_ $$00000-0001-9547-5508$$aRodriguez-Vita, Juan$$b17$$eLast author
000275610 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-023-38064-w$$gVol. 14, no. 1, p. 2353$$n1$$p2353$$tNature Communications$$v14$$x2041-1723$$y2023
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