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Trefoil Factor 1 Stimulates Both Pancreatic Cancer and Stellate Cells and Increases Metastasis

Lookup NU author(s): Dr Felicity May, Professor Bruce Westley

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Abstract

Objectives: Trefoil factor 1 (TFF1) is a stable secretory protein expressed widely in the gastrointestinal mucosa that is also expressed in pancreatic ductal adenocarcinoma (PDAC). In the current study, we documented the extent and timing of TFF1 expression and investigated the effects of TFF1 on PDAC cells and stellate cells, the primary cells of the PDAC stroma. Methods: Trefoil factor 1 expression in pancreatic cancer tissues and cell lines was analyzed using microarray, quantitative reverse transcriptase-polymerase chain reaction, and immunohistochemistry. The effects of recombinant TFF1 on cell growth, migration, and invasion of pancreatic cancer cell lines and immortalized human pancreatic stellate cells (HPSCs) were analyzed using MTS and Matrigel-coated invasion chambers. In vivo studies were also conducted in which Mpanc-96 cells stably expressing TFF1 were implanted orthotopically into nude mice. Results: Trefoil factor 1 was highly increased in preneoplastic lesions. Recombinant TFF1 stimulated motility of both cancer and HPSCs. In contrast, only HPSC cell growth was increased by TFF1. In vivo studies showed that overexpression of TFF1 in PDAC cells did not affect primary tumor growth but greatly increased metastasis. Conclusions: The present data demonstrate that TFF1 influences both PDAC cells and stellate cells and stimulates metastasis.


Publication metadata

Author(s): Arumugam T, Brandt W, Ramachandran V, Moore TT, Wang HM, May FE, Westley BR, Hwang RF, Logsdon CD

Publication type: Article

Publication status: Published

Journal: Pancreas

Year: 2011

Volume: 40

Issue: 6

Pages: 815-822

Print publication date: 01/08/2011

ISSN (print): 0885-3177

ISSN (electronic): 1536-4828

Publisher: Lippincott Williams & Wilkins

URL: http://dx.doi.org/10.1097/MPA.0b013e31821f6927

DOI: 10.1097/MPA.0b013e31821f6927


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Funding

Funder referenceFunder name
P20 CA101936MD Anderson Pancreatic Specialized Programs of Research Excellence
Lockton Endowment
CA16672MD Anderson Support Core
DK56338Public Health Service

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