Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma

Sonic hedgehog (Shh), a soluble ligand overexpressed by neoplastic cells in pancreatic ductal adenocarcinoma (PDAC), drives formation of a fibroblast-rich desmoplastic stroma. To better understand its role in malignant progression, we deleted Shh in a well-defined mouse model of PDAC. As predicted,...

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Autores: Rhim, A.D. (Andrew D.)|||/items/8f30f7a0-11f5-4445-b8e8-a1ea3007c601, Oberstein, P.E. (Paul E.)|||/items/4ab1f0d5-5aa8-4f67-9098-e84519ef17dd, Thomas, D.H. (Dafydd H.)|||/items/53634925-f275-434f-bd50-93f617f704b1, Mirek, E.T. (Emily T.)|||/items/ddd8e77e-2402-4305-a0dd-a43da18168db, Palermo, C.F. (Carmine F.)|||/items/d08f4afc-0112-4909-ab01-018a1afad6b4, Sastra, S.A.(Stephen A.)|||/items/d9d451a8-6cd2-4b72-8b91-1d675d97f7a6, Dekleva, E.N. (Erin N.)|||/items/bf52e814-ed77-4d70-b630-366415ef1691, Saunders, T. (Tyler)|||/items/7e143e79-623a-473f-882a-706ff0fc3965, Becerra, C.P. (Claudia P.)|||/items/2a0b3146-d204-4d18-8560-750530360705, Tattersall, I.W. (Ian W.)|||/items/f635232f-8fb8-4a0d-b872-5ccd2f9d7076, Westphalen, C.B. (Christoph Benedikt)|||/items/62d44a3e-9aeb-4546-a0d8-4131c3a2f81a, Kitajewski, J. (Jan)|||/items/2f6ba8bd-e58e-431e-a77a-397978046171, García-Fernández-de-Barrena, M. (Maite)|||/items/cfa77580-40b9-43a4-b237-b234ef7fb6cb, Fernandez-Zapico, M.E. (Martín E.)|||/items/4c4f76f4-afec-47be-91c9-c67d0d54ac41, Iacobuzio-Donahue, C. (Christine)|||/items/8312ffaf-0d67-41dd-be6a-f6d543c27abc, Olive, K.P. (Kenneth P.)|||/items/c3eeb8ba-6f10-4908-8851-3865db57f527, Stanger, B.Z. (Ben Z.)|||/items/a1285483-5c16-45a6-9fb2-ba919772c8c5
Formato: artículo
Fecha de publicación:2014
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/121108
Acesso em linha:https://hdl.handle.net/10171/121108
Access Level:acceso abierto
Palavra-chave:Pancreatic ductal adenocarcinoma
Stromal elements
Descrição
Resumo:Sonic hedgehog (Shh), a soluble ligand overexpressed by neoplastic cells in pancreatic ductal adenocarcinoma (PDAC), drives formation of a fibroblast-rich desmoplastic stroma. To better understand its role in malignant progression, we deleted Shh in a well-defined mouse model of PDAC. As predicted, Shh-deficient tumors had reduced stromal content. Surprisingly, such tumors were more aggressive and exhibited undifferentiated histology, increased vascularity, and heightened proliferation--features that were fully recapitulated in control mice treated with a Smoothened inhibitor. Furthermore, administration of VEGFR blocking antibody selectively improved survival of Shh-deficient tumors, indicating that Hedgehog-driven stroma suppresses tumor growth in part by restraining tumor angiogenesis. Together, these data demonstrate that some components of the tumor stroma can act to restrain tumor growth.

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