Recent studies have identified organ-specific receptors on the luminal surface of the microvascular endothelium that are specifically recognized by tumor cell ligands, thereby facilitating tumor cell arrest and transmigration into the extravascular space (3, 4). The evidence suggests that this attachment precedes and is required for tumor cell extravasation and subsequent invasion into the target organ parenchyma. The attachment of circulating tumor cells to the vascular endothelium of the target organ is thought to be one key step in the metastatic cascade (2).

The ability of disseminated cancer cells to establish metastases in secondary organs is regulated by a combination of factors including access to the organ microvasculature (hemodynamic factors) and specific host-tumor cell interactions (reviewed in Ref. 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. M-27 cells failed to induce cytokine or E-selectin expression, whereas B-16 cells elicited a delayed and more short-lived response. In situ hybridization analysis and immunohistochemistry localized E-selectin mRNA and protein, respectively, to the sinusoidal endothelium. 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. Rapid cytokine mRNA induction was noted within 30–60 min of H-59 injection, reaching maximal levels at 4–6 h. In livers derived from normal or saline-injected mice, only minimal basal levels of TNF-α and IL-1 mRNA were detectable by RT-PCR. 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. 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. 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.

The cytokine-inducible endothelial cell adhesion receptor E-selectin has been implicated in cancer metastasis.

Rapid Response by D.J. Jamison