Crosstalk between mast cells and pancreatic cancer cells contributes to pancreatic tumor progression

Matthew J. Strouch, Eric C. Cheon, Mohammad R. Salabat, Seth B. Krantz, Elias Gounaris, Laleh G. Melstrom, Surabhi Dangi-Garimella, Edward Wang, Hidayatullah G. Munshi, Khashayarsha Khazaie, David J. Bentrem

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

Purpose: To assess the clinical and pathologic significance of mast cell infiltration in human pancreatic cancer and evaluate crosstalk between mast cells and cancer cells in vitro. Experimental Design: Immunohistochemistry for tryptase was done on 53 pancreatic cancer specimens. Mast cell counts were correlated with clinical variables and survival. Serum tryptase activity from patients with cancer was compared with patients with benign pancreatic disease. In vitro, the effect of pancreatic cancer-conditioned medium on mast cell migration was assessed. The effect of conditioned medium from the human mast cell line, LAD-2, on cancer and normal ductal cell proliferation was assessed by thymidine incorporation. Matrigel invasion assays were used to evaluate the effect of mast cell-conditioned medium on cancer cell invasion in the presence and absence of a matrix metalloproteinase inhibitor, GM6001. Results: Mast cell infiltration was significantly increased in pancreatic cancer compared with normal pancreatic tissue (11.4 ± 6.7 versus 2.0 ± 1.4, P < 0.001). Increased infiltrating mast cells correlated with higher grade tumors (P < 0.0001) and worse survival. Patients with pancreatic cancer had elevated serum tryptase activity (P < 0.05). In vitro, AsPC1 and PANC-1 cells induced mast cell migration. Mast cell-conditioned medium induced pancreatic cancer cell migration, proliferation, and invasion but had no effect on normal ductal cells. Furthermore, the effect of mast cells on cancer cell invasion was, in large part, matrix metalloproteinase-dependent. Conclusions: Tumor-infiltrating mast cells are associated with worse prognosis in pancreatic cancer. In vitro, the interaction between mast cells and pancreatic cancer cells promotes tumor growth and invasion.

Original languageEnglish (US)
Pages (from-to)2257-2265
Number of pages9
JournalClinical Cancer Research
Volume16
Issue number8
DOIs
StatePublished - Apr 15 2010

Fingerprint

Pancreatic Neoplasms
Mast Cells
Neoplasms
Conditioned Culture Medium
Tryptases
Cell Movement
Cell Proliferation
Pancreatic Diseases
Matrix Metalloproteinase Inhibitors
Survival
Serum
Matrix Metalloproteinases
Thymidine
Research Design
Cell Count
Immunohistochemistry

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Strouch, Matthew J. ; Cheon, Eric C. ; Salabat, Mohammad R. ; Krantz, Seth B. ; Gounaris, Elias ; Melstrom, Laleh G. ; Dangi-Garimella, Surabhi ; Wang, Edward ; Munshi, Hidayatullah G. ; Khazaie, Khashayarsha ; Bentrem, David J. / Crosstalk between mast cells and pancreatic cancer cells contributes to pancreatic tumor progression. In: Clinical Cancer Research. 2010 ; Vol. 16, No. 8. pp. 2257-2265.
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abstract = "Purpose: To assess the clinical and pathologic significance of mast cell infiltration in human pancreatic cancer and evaluate crosstalk between mast cells and cancer cells in vitro. Experimental Design: Immunohistochemistry for tryptase was done on 53 pancreatic cancer specimens. Mast cell counts were correlated with clinical variables and survival. Serum tryptase activity from patients with cancer was compared with patients with benign pancreatic disease. In vitro, the effect of pancreatic cancer-conditioned medium on mast cell migration was assessed. The effect of conditioned medium from the human mast cell line, LAD-2, on cancer and normal ductal cell proliferation was assessed by thymidine incorporation. Matrigel invasion assays were used to evaluate the effect of mast cell-conditioned medium on cancer cell invasion in the presence and absence of a matrix metalloproteinase inhibitor, GM6001. Results: Mast cell infiltration was significantly increased in pancreatic cancer compared with normal pancreatic tissue (11.4 ± 6.7 versus 2.0 ± 1.4, P < 0.001). Increased infiltrating mast cells correlated with higher grade tumors (P < 0.0001) and worse survival. Patients with pancreatic cancer had elevated serum tryptase activity (P < 0.05). In vitro, AsPC1 and PANC-1 cells induced mast cell migration. Mast cell-conditioned medium induced pancreatic cancer cell migration, proliferation, and invasion but had no effect on normal ductal cells. Furthermore, the effect of mast cells on cancer cell invasion was, in large part, matrix metalloproteinase-dependent. Conclusions: Tumor-infiltrating mast cells are associated with worse prognosis in pancreatic cancer. In vitro, the interaction between mast cells and pancreatic cancer cells promotes tumor growth and invasion.",
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Crosstalk between mast cells and pancreatic cancer cells contributes to pancreatic tumor progression. / Strouch, Matthew J.; Cheon, Eric C.; Salabat, Mohammad R.; Krantz, Seth B.; Gounaris, Elias; Melstrom, Laleh G.; Dangi-Garimella, Surabhi; Wang, Edward; Munshi, Hidayatullah G.; Khazaie, Khashayarsha; Bentrem, David J.

In: Clinical Cancer Research, Vol. 16, No. 8, 15.04.2010, p. 2257-2265.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Crosstalk between mast cells and pancreatic cancer cells contributes to pancreatic tumor progression

AU - Strouch, Matthew J.

AU - Cheon, Eric C.

AU - Salabat, Mohammad R.

AU - Krantz, Seth B.

AU - Gounaris, Elias

AU - Melstrom, Laleh G.

AU - Dangi-Garimella, Surabhi

AU - Wang, Edward

AU - Munshi, Hidayatullah G.

AU - Khazaie, Khashayarsha

AU - Bentrem, David J.

PY - 2010/4/15

Y1 - 2010/4/15

N2 - Purpose: To assess the clinical and pathologic significance of mast cell infiltration in human pancreatic cancer and evaluate crosstalk between mast cells and cancer cells in vitro. Experimental Design: Immunohistochemistry for tryptase was done on 53 pancreatic cancer specimens. Mast cell counts were correlated with clinical variables and survival. Serum tryptase activity from patients with cancer was compared with patients with benign pancreatic disease. In vitro, the effect of pancreatic cancer-conditioned medium on mast cell migration was assessed. The effect of conditioned medium from the human mast cell line, LAD-2, on cancer and normal ductal cell proliferation was assessed by thymidine incorporation. Matrigel invasion assays were used to evaluate the effect of mast cell-conditioned medium on cancer cell invasion in the presence and absence of a matrix metalloproteinase inhibitor, GM6001. Results: Mast cell infiltration was significantly increased in pancreatic cancer compared with normal pancreatic tissue (11.4 ± 6.7 versus 2.0 ± 1.4, P < 0.001). Increased infiltrating mast cells correlated with higher grade tumors (P < 0.0001) and worse survival. Patients with pancreatic cancer had elevated serum tryptase activity (P < 0.05). In vitro, AsPC1 and PANC-1 cells induced mast cell migration. Mast cell-conditioned medium induced pancreatic cancer cell migration, proliferation, and invasion but had no effect on normal ductal cells. Furthermore, the effect of mast cells on cancer cell invasion was, in large part, matrix metalloproteinase-dependent. Conclusions: Tumor-infiltrating mast cells are associated with worse prognosis in pancreatic cancer. In vitro, the interaction between mast cells and pancreatic cancer cells promotes tumor growth and invasion.

AB - Purpose: To assess the clinical and pathologic significance of mast cell infiltration in human pancreatic cancer and evaluate crosstalk between mast cells and cancer cells in vitro. Experimental Design: Immunohistochemistry for tryptase was done on 53 pancreatic cancer specimens. Mast cell counts were correlated with clinical variables and survival. Serum tryptase activity from patients with cancer was compared with patients with benign pancreatic disease. In vitro, the effect of pancreatic cancer-conditioned medium on mast cell migration was assessed. The effect of conditioned medium from the human mast cell line, LAD-2, on cancer and normal ductal cell proliferation was assessed by thymidine incorporation. Matrigel invasion assays were used to evaluate the effect of mast cell-conditioned medium on cancer cell invasion in the presence and absence of a matrix metalloproteinase inhibitor, GM6001. Results: Mast cell infiltration was significantly increased in pancreatic cancer compared with normal pancreatic tissue (11.4 ± 6.7 versus 2.0 ± 1.4, P < 0.001). Increased infiltrating mast cells correlated with higher grade tumors (P < 0.0001) and worse survival. Patients with pancreatic cancer had elevated serum tryptase activity (P < 0.05). In vitro, AsPC1 and PANC-1 cells induced mast cell migration. Mast cell-conditioned medium induced pancreatic cancer cell migration, proliferation, and invasion but had no effect on normal ductal cells. Furthermore, the effect of mast cells on cancer cell invasion was, in large part, matrix metalloproteinase-dependent. Conclusions: Tumor-infiltrating mast cells are associated with worse prognosis in pancreatic cancer. In vitro, the interaction between mast cells and pancreatic cancer cells promotes tumor growth and invasion.

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