Rapid induction of cytokine and E-selectin expression in the liver in response to metastatic tumor cells.
The cytokine-inducible endothelial cell adhesion receptor E-selectin has been implicated in cancer metastasis. Previously, we reported that experimental liver metastasis of Lewis lung carcinoma subline H-59 cells could be abrogated in animals treated with an anti-E-selectin antibody. To gain further insight into the functional relevance of E-selectin expression to liver colonization, we investigated here the time course of cytokine and hepatic E-selectin expression after the intrasplenic/portal inoculation of H-59 cells by using a combination of reverse transcription-PCR, Northern blot analysis, immunohistochemistry, and in situ hybridization. In parallel, we analyzed cytokine induction in response to the injection of Lewis lung carcinoma subline M-27 and murine melanoma B16-F1 cells, which do not spontaneously metastasize to the liver. In livers derived from normal or saline-injected mice, only minimal basal levels of TNF-alpha and IL-1 mRNA were detectable by RT-PCR. Rapid cytokine mRNA induction was noted within 30-60 min of H-59 injection, reaching maximal levels at 4-6 h. This was followed by the appearance of E-selectin mRNA, which was detectable at 2 h after injection and reached maximal levels at 6-8 h, declining to basal levels by 24 h. In situ hybridization analysis and immunohistochemistry localized E-selectin mRNA and protein, respectively, to the sinusoidal endothelium. M-27 cells failed to induce cytokine or E-selectin expression, whereas B-16 cells elicited a delayed and more short-lived response. The results demonstrate that upon entry into the hepatic circulation, tumor cells can rapidly trigger a molecular cascade leading to the induction of E-selectin expression on the sinusoidal endothelium and suggest that E-selectin induction may contribute to the liver-colonizing potential of tumor cells.
Khatib
A M
AM
Department of Surgery, McGill University and the Royal Victoria Hospital, Montreal, Quebec, Canada.
Kontogiannea
M
M
Fallavollita
L
L
Jamison
B
B
Meterissian
S
S
Brodt
P
P
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000473:pathology / Q000556:secondary; D016207:Cytokines / Q000096:biosynthesis*; D019040:E-Selectin / Q000096:biosynthesis*; D004727:Endothelium / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007375:Interleukin-1 / Q000096:biosynthesis; D008114:Liver Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D008546:Melanoma, Experimental / Q000473:pathology / Q000556:secondary; D051379:Mice; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D019040:E-Selectin; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha