The host inflammatory response promotes liver metastasis by increasing tumor cell arrest and extravasation.
Inflammation can play a regulatory role in cancer progression and metastasis. Previously, we have shown that metastatic tumor cells entering the liver trigger a proinflammatory response involving Kupffer cell-mediated release of tumor necrosis factor-alpha and the up-regulation of vascular endothelial cell adhesion receptors, such as E-selectin. Here, we analyzed spatio-temporal aspects of the ensuing tumor-endothelial cell interaction using human colorectal carcinoma CX-1 and murine carcinoma H-59 cells and a combination of immunohistochemistry, confocal microscopy, and three-dimensional reconstruction. E-selectin expression was evident mainly on sinusoidal vessels by 6 and 10 hours, respectively, following H-59 and CX-1 inoculation, and this corresponded to a stabilization of the number of tumor cells within the sinuses. Tumor cells arrested in E-selectin(+) vessels and appeared to flatten and traverse the vessel lining, away from sites of intense E-selectin staining. This process was evident by 8 (H-59) and 12 (CX-1) hours after inoculation, coincided with increased endothelial vascular cell adhesion molecule-1 expression, and involved tumor cell attachment in areas of intense vascular cell adhesion molecule-1 and platelet endothelial cell adhesion molecule-1 expression. Nonmetastatic (human) MIP-101 and (murine) M-27 cells induced a weaker response and could not be seen to extravasate. The results show that metastatic tumor cells can alter the hepatic microvasculature and use newly expressed endothelial cell receptors to arrest and extravasate.
Auguste
Patrick
P
Department of Surgery, McGill University Health Cener and Royal Victoria Hospital, Quebec, Canada.
Fallavollita
Lucia
L
Wang
Ni
N
Burnier
Julia
J
Bikfalvi
Andreas
A
Brodt
Pnina
P
D000818:Animals; D018827:Carcinoma, Lewis Lung; D002450:Cell Communication; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D019040:E-Selectin / Q000096:biosynthesis; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000473:pathology*; D007728:Kupffer Cells / Q000378:metabolism*; D008099:Liver / Q000098:blood supply; D008113:Liver Neoplasms / Q000276:immunology / Q000556:secondary*; D051379:Mice; D018613:Microscopy, Confocal; D009361:Neoplasm Invasiveness / Q000473:pathology*
D016207:Cytokines; D019040:E-Selectin