Mast cells in tumor microenvironment promotes the in vivo growth of pancreatic ductal adenocarcinoma

David Z. Chang, Ying Ma, Baoan D Ji, Huamin Wang, Defeng Deng, Yan Liu, James L. Abbruzzese, Yong Jun Liu, Craig D. Logsdon, Patrick Hwu

Research output: Contribution to journalArticle

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Abstract

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer death. No effective therapy is currently available for PDAC because of the lack of understanding of the mechanisms leading to its growth and development. Inflammatory cells, particularly mast cells, have been shown to play key roles in some cancers. We carried out this study to test the hypothesis that mast cells in the tumor microenvironment are essential for PDAC tumorigenesis. Experimental Design: The presence of inflammatory cells at various stages of PDAC development was determined in a spontaneous mouse model of PDAC (K-ras G12V). The importance of mast cells was determined using orthotopically implanted PDAC cells in mast cell-deficient Kit w-sh/w-sh mice and further confirmed by reconstitution of wild-type bone marrow-derived mast cells. Clinical relevance was assessed by correlating the presence of mast cells with clinical outcome in patients with PDAC. Results: In the spontaneous mouse model of PDAC (K-ras G12V), there was an early influx of mast cells to the tumor microenvironment. PDAC tumor growth was suppressed in mast cell-deficient Kit w-sh/w-sh mice, but aggressive PDAC growth was restored when PDAC cells were injected into mast cell-deficient mice reconstituted with wild-type bone marrow-derived mast cells. Mast cell infiltration into the tumor microenvironment was predictive of poor prognosis in patients with PDAC. Conclusions: Mast cells play an important role in PDAC growth and development in mouse models and are indicative of poor prognosis in humans, which makes them a potential novel therapeutic target.

Original languageEnglish (US)
Pages (from-to)7015-7023
Number of pages9
JournalClinical Cancer Research
Volume17
Issue number22
DOIs
StatePublished - Nov 15 2011
Externally publishedYes

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Tumor Microenvironment
Mast Cells
Adenocarcinoma
Growth
Growth and Development
Bone Marrow
Neoplasms
Cause of Death
Carcinogenesis
Research Design

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Mast cells in tumor microenvironment promotes the in vivo growth of pancreatic ductal adenocarcinoma. / Chang, David Z.; Ma, Ying; Ji, Baoan D; Wang, Huamin; Deng, Defeng; Liu, Yan; Abbruzzese, James L.; Liu, Yong Jun; Logsdon, Craig D.; Hwu, Patrick.

In: Clinical Cancer Research, Vol. 17, No. 22, 15.11.2011, p. 7015-7023.

Research output: Contribution to journalArticle

Chang, DZ, Ma, Y, Ji, BD, Wang, H, Deng, D, Liu, Y, Abbruzzese, JL, Liu, YJ, Logsdon, CD & Hwu, P 2011, 'Mast cells in tumor microenvironment promotes the in vivo growth of pancreatic ductal adenocarcinoma', Clinical Cancer Research, vol. 17, no. 22, pp. 7015-7023. https://doi.org/10.1158/1078-0432.CCR-11-0607
Chang, David Z. ; Ma, Ying ; Ji, Baoan D ; Wang, Huamin ; Deng, Defeng ; Liu, Yan ; Abbruzzese, James L. ; Liu, Yong Jun ; Logsdon, Craig D. ; Hwu, Patrick. / Mast cells in tumor microenvironment promotes the in vivo growth of pancreatic ductal adenocarcinoma. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 22. pp. 7015-7023.
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abstract = "Purpose: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer death. No effective therapy is currently available for PDAC because of the lack of understanding of the mechanisms leading to its growth and development. Inflammatory cells, particularly mast cells, have been shown to play key roles in some cancers. We carried out this study to test the hypothesis that mast cells in the tumor microenvironment are essential for PDAC tumorigenesis. Experimental Design: The presence of inflammatory cells at various stages of PDAC development was determined in a spontaneous mouse model of PDAC (K-ras G12V). The importance of mast cells was determined using orthotopically implanted PDAC cells in mast cell-deficient Kit w-sh/w-sh mice and further confirmed by reconstitution of wild-type bone marrow-derived mast cells. Clinical relevance was assessed by correlating the presence of mast cells with clinical outcome in patients with PDAC. Results: In the spontaneous mouse model of PDAC (K-ras G12V), there was an early influx of mast cells to the tumor microenvironment. PDAC tumor growth was suppressed in mast cell-deficient Kit w-sh/w-sh mice, but aggressive PDAC growth was restored when PDAC cells were injected into mast cell-deficient mice reconstituted with wild-type bone marrow-derived mast cells. Mast cell infiltration into the tumor microenvironment was predictive of poor prognosis in patients with PDAC. Conclusions: Mast cells play an important role in PDAC growth and development in mouse models and are indicative of poor prognosis in humans, which makes them a potential novel therapeutic target.",
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AU - Chang, David Z.

AU - Ma, Ying

AU - Ji, Baoan D

AU - Wang, Huamin

AU - Deng, Defeng

AU - Liu, Yan

AU - Abbruzzese, James L.

AU - Liu, Yong Jun

AU - Logsdon, Craig D.

AU - Hwu, Patrick

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N2 - Purpose: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer death. No effective therapy is currently available for PDAC because of the lack of understanding of the mechanisms leading to its growth and development. Inflammatory cells, particularly mast cells, have been shown to play key roles in some cancers. We carried out this study to test the hypothesis that mast cells in the tumor microenvironment are essential for PDAC tumorigenesis. Experimental Design: The presence of inflammatory cells at various stages of PDAC development was determined in a spontaneous mouse model of PDAC (K-ras G12V). The importance of mast cells was determined using orthotopically implanted PDAC cells in mast cell-deficient Kit w-sh/w-sh mice and further confirmed by reconstitution of wild-type bone marrow-derived mast cells. Clinical relevance was assessed by correlating the presence of mast cells with clinical outcome in patients with PDAC. Results: In the spontaneous mouse model of PDAC (K-ras G12V), there was an early influx of mast cells to the tumor microenvironment. PDAC tumor growth was suppressed in mast cell-deficient Kit w-sh/w-sh mice, but aggressive PDAC growth was restored when PDAC cells were injected into mast cell-deficient mice reconstituted with wild-type bone marrow-derived mast cells. Mast cell infiltration into the tumor microenvironment was predictive of poor prognosis in patients with PDAC. Conclusions: Mast cells play an important role in PDAC growth and development in mouse models and are indicative of poor prognosis in humans, which makes them a potential novel therapeutic target.

AB - Purpose: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer death. No effective therapy is currently available for PDAC because of the lack of understanding of the mechanisms leading to its growth and development. Inflammatory cells, particularly mast cells, have been shown to play key roles in some cancers. We carried out this study to test the hypothesis that mast cells in the tumor microenvironment are essential for PDAC tumorigenesis. Experimental Design: The presence of inflammatory cells at various stages of PDAC development was determined in a spontaneous mouse model of PDAC (K-ras G12V). The importance of mast cells was determined using orthotopically implanted PDAC cells in mast cell-deficient Kit w-sh/w-sh mice and further confirmed by reconstitution of wild-type bone marrow-derived mast cells. Clinical relevance was assessed by correlating the presence of mast cells with clinical outcome in patients with PDAC. Results: In the spontaneous mouse model of PDAC (K-ras G12V), there was an early influx of mast cells to the tumor microenvironment. PDAC tumor growth was suppressed in mast cell-deficient Kit w-sh/w-sh mice, but aggressive PDAC growth was restored when PDAC cells were injected into mast cell-deficient mice reconstituted with wild-type bone marrow-derived mast cells. Mast cell infiltration into the tumor microenvironment was predictive of poor prognosis in patients with PDAC. Conclusions: Mast cells play an important role in PDAC growth and development in mouse models and are indicative of poor prognosis in humans, which makes them a potential novel therapeutic target.

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