MUC4-expressing pancreatic adenocarcinomas show elevated levels of both T H 1 and T H 2 cytokines

Potential pathobiologic implications

Mahefatiana Andrianifahanana, Subhash Chauhan, Amit Choudhury, Nicolas Moniaux, Randall E. Brand, Aaron A. Sasson, Parviz M. Pour, Surinder K. Batra

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 H 1) 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 H 1 and T H 2 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 H 1 and T H 2 signaling in the pancreatic tumor microenvironment. These findings may provide useful insights into the pathobiology of pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)2319-2329
Number of pages11
JournalAmerican Journal of Gastroenterology
Volume101
Issue number10
DOIs
StatePublished - Oct 1 2006
Externally publishedYes

Fingerprint

Interferons
Adenocarcinoma
Cytokines
Tumor Cell Line
Pancreatic Neoplasms
Neoplasms
Tumor Microenvironment
Transforming Growth Factors
Mucins
Interleukin-12
Helper-Inducer T-Lymphocytes
Tretinoin
Interleukin-10
Reverse Transcription
Interleukin-2
Cell Line
Polymerase Chain Reaction
Proteins

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

MUC4-expressing pancreatic adenocarcinomas show elevated levels of both T H 1 and T H 2 cytokines : Potential pathobiologic implications. / Andrianifahanana, Mahefatiana; Chauhan, Subhash; Choudhury, Amit; Moniaux, Nicolas; Brand, Randall E.; Sasson, Aaron A.; Pour, Parviz M.; Batra, Surinder K.

In: American Journal of Gastroenterology, Vol. 101, No. 10, 01.10.2006, p. 2319-2329.

Research output: Contribution to journalArticle

Andrianifahanana, Mahefatiana ; Chauhan, Subhash ; Choudhury, Amit ; Moniaux, Nicolas ; Brand, Randall E. ; Sasson, Aaron A. ; Pour, Parviz M. ; Batra, Surinder K. / MUC4-expressing pancreatic adenocarcinomas show elevated levels of both T H 1 and T H 2 cytokines : Potential pathobiologic implications. In: American Journal of Gastroenterology. 2006 ; Vol. 101, No. 10. pp. 2319-2329.
@article{211059c54e3d466d9ad5e2c37661ca5d,
title = "MUC4-expressing pancreatic adenocarcinomas show elevated levels of both T H 1 and T H 2 cytokines: Potential pathobiologic implications",
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 H 1) 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 H 1 and T H 2 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 H 1 and T H 2 signaling in the pancreatic tumor microenvironment. These findings may provide useful insights into the pathobiology of pancreatic cancer.",
author = "Mahefatiana Andrianifahanana and Subhash Chauhan and Amit Choudhury and Nicolas Moniaux and Brand, {Randall E.} and Sasson, {Aaron A.} and Pour, {Parviz M.} and Batra, {Surinder K.}",
year = "2006",
month = "10",
day = "1",
doi = "10.1111/j.1572-0241.2006.00871.x",
language = "English (US)",
volume = "101",
pages = "2319--2329",
journal = "American Journal of Gastroenterology",
issn = "0002-9270",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - MUC4-expressing pancreatic adenocarcinomas show elevated levels of both T H 1 and T H 2 cytokines

T2 - Potential pathobiologic implications

AU - Andrianifahanana, Mahefatiana

AU - Chauhan, Subhash

AU - Choudhury, Amit

AU - Moniaux, Nicolas

AU - Brand, Randall E.

AU - Sasson, Aaron A.

AU - Pour, Parviz M.

AU - Batra, Surinder K.

PY - 2006/10/1

Y1 - 2006/10/1

N2 - 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 H 1) 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 H 1 and T H 2 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 H 1 and T H 2 signaling in the pancreatic tumor microenvironment. These findings may provide useful insights into the pathobiology of pancreatic cancer.

AB - 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 H 1) 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 H 1 and T H 2 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 H 1 and T H 2 signaling in the pancreatic tumor microenvironment. These findings may provide useful insights into the pathobiology of pancreatic cancer.

UR - http://www.scopus.com/inward/record.url?scp=33749170127&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33749170127&partnerID=8YFLogxK

U2 - 10.1111/j.1572-0241.2006.00871.x

DO - 10.1111/j.1572-0241.2006.00871.x

M3 - Article

VL - 101

SP - 2319

EP - 2329

JO - American Journal of Gastroenterology

JF - American Journal of Gastroenterology

SN - 0002-9270

IS - 10

ER -