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


METHODS
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.
Strouch
Matthew J
MJ
Department of Surgery, The Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, and Jesse Brown VA Medical Center, Chicago, Illinois, USA.
Cheon
Eric C
EC
Salabat
Mohammad R
MR
Krantz
Seth B
SB
Gounaris
Elias
E
Melstrom
Laleh G
LG
Dangi-Garimella
Surabhi
S
Wang
Edward
E
Munshi
Hidayatullah G
HG
Khazaie
Khashayarsha
K
Bentrem
David J
DJ
D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002291:Carcinoma, Papillary / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D017077:Culture Media, Conditioned / Q000494:pharmacology; D018282:Cystadenocarcinoma, Mucinous / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D015996:Survival Rate; D053802:Tryptases / Q000097:blood
D017077:Culture Media, Conditioned; D053802:Tryptases