Coexisting macrophage-associated fibrin formation and tumor cell urokinase in squamous cell and adenocarcinoma of the lung tissues.
Mechanisms of coagulation activation in situ were studied by means of immunohistochemical techniques applied to surgically resected primary adenocarcinomas and squamous cell carcinomas of the lung. Findings in these two histologic types were similar. Double-labeling techniques using macrophage-specific antibody together with antibody to either tissue factor, factor VII, factor X, or factor V revealed coincident staining for each of these coagulation factors on tumor-associated macrophages. Staining of tumor cells for these factors was rare and inconsistent. Both macrophages and fibroblasts in the tumor connective tissue stained for the a subunit of factor XIII. Fibrinogen was abundant throughout the tumor connective tissue, but staining for fibrin and D-dimer cross-linked sites of fibrin was restricted to areas adjacent to macrophages, indicating that thrombin was generated in association with tumor macrophages but not with tumor cells. By contrast, tumor cells stained diffusely for urokinase-type plasminogen activator and focally for thrombomodulin. These findings contrast with those reported previously for small cell carcinoma of the lung and suggest that coagulation activation in adenocarcinoma and squamous cell carcinoma of the lung may occur indirectly through activation of certain host cells such as macrophages. By contrast, tumor cell plasminogen activator may mediate certain aspects of the malignant phenotype in these tumor types.
Ornstein
D L
DL
Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire.
Zacharski
L R
LR
Memoli
V A
VA
Kisiel
W
W
Kudryk
B J
BJ
Hunt
J
J
Rousseau
S M
SM
Stump
D C
DC
D000230:Adenocarcinoma / Q000097:blood* / Q000201:enzymology / Q000378:metabolism; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000032:analysis; D001777:Blood Coagulation / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000201:enzymology / Q000378:metabolism; D005337:Fibrin / Q000096:biosynthesis* / Q000502:physiology; D005342:Fibrinolysis / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000097:blood* / Q000201:enzymology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D013917:Thrombin / Q000096:biosynthesis; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood*
D000951:Antigens, Neoplasm; D005337:Fibrin; D013917:Thrombin; D014568:Urokinase-Type Plasminogen Activator