IngentaConnect MUC4-Expressing Pancreatic Adenocarcinomas Show Elevated Levels o...

Authors: Andrianifahanana, Mahefatiana¹; Chauhan, Subhash C.¹; Choudhury, Amit¹; Moniaux, Nicolas¹; Brand, Randall E.²; Sasson, Aaron A.³; Pour, Parviz M.; Batra, Surinder K.

Source: The American Journal of Gastroenterology, Volume 101, Number 10, October 2006 , pp. 2319-2329(11)

Publisher: Blackwell Publishing

Abstract:

OBJECTIVE: The human MUC4 mucin plays an important role in the pathogenesis of pancreatic cancer. Recently, we have demonstrated that MUC4 expression in pancreatic tumor cells is regulated by interferon-γ (IFNγ) and by retinoic acid via transforming growth factor β 2 (TGFβ-2). In the present study, we established the pathobiological association of various cytokines and MUC4 in pancreatic tumor tissues and tumor cell lines.

METHODS: Using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and/or immunohistochemical analyses, we examined the expression of MUC4, IFNγ, TGFβs, and several immunologically relevant cytokines in a panel of 11 pancreatic adenocarcinomas (PA), three normal pancreatic (NP) tissue specimens, and 11 pancreatic tumor cell lines.

RESULTS: Our data revealed that both MUC4 and IFNγ were expressed at moderate to high levels in the majority of PA, while being undetectable in NP. Moreover, transcript for interleukin 2 (IL-2), a known marker of activated T helper 1 (T_H1) lymphocytes, exhibited an expression profile similar to IFNγ, suggesting a role of these immune effector cells as a potential source of IFNγ in PA. Of note, IFNγ protein was detected in the inflamed tissues neighboring tumor areas. Furthermore, TGFβs were expressed by most cell lines and frequently upregulated in PA compared with NP. Interestingly, both IL-12 and IL-10, two key cytokines of the T_H1 and T_H2 pathways, respectively, were expressed at higher levels in PA relative to NP.

CONCLUSIONS: These observations support the potential implication of IFNγ and TGFβs in MUC4 regulation in vivo and suggest a complex interaction of T_H1 and T_H2 signaling in the pancreatic tumor microenvironment. These findings may provide useful insights into the pathobiology of pancreatic cancer.

(Am J Gastroenterol 2006;101:2319-2329)

Document Type: Research article

DOI: 10.1111/j.1572-0241.2006.00871.x

Affiliations: 1: Department of Biochemistry and Molecular Biology 2: Northwestern University Feinberg School of Medicine, Division of Gastroenterology, Evanston Northwestern Healthcare, Evanston, Illinois. 3: Department of Surgery, University of Nebraska Medical Center

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MUC4-Expressing Pancreatic Adenocarcinomas Show Elevated Levels of Both TH1 and TH2 Cytokines: Potential Pathobiologic Implications

MUC4-Expressing Pancreatic Adenocarcinomas Show Elevated Levels of Both T_H1 and T_H2 Cytokines: Potential Pathobiologic Implications