Binding of gastrointestinal tumor cells to endothelial E- and P-selectin adhesion receptors leads to transient down-regulation of sLeX ligands in vitro.

BACKGROUND AND AIMS: The prognostic relevance of sialyl Lewis X (sLeX) expression in colorectal and gastric cancer and its relevance to the hematogenous phase of tumor invasion is controversial. This study was designed to evaluate sLeX expression during tumor cell-endothelial cell interaction in vitro. METHODS: Adhesion and transendothelial penetration of MKN45, PaCa-2, WiDr, or Dan-G cells was analyzed by combined phase contrast-reflection interference contrast microscopy. In parallel, kinetics of membranous sLeX expression were examined fluorimetrically. To identify factor(s) which may be responsible for sLeX expression during tumor invasion tumor cells were treated with soluble immunomodulators, isolated endothelial plasma membranes, or E-selectin or P-selectin IgG fusion proteins. sLeX was then analyzed by flow cytometry. RESULTS: Fluorometric quantification of sLeX demonstrated an inverse correlation between basal sLeX expression level and adhesion capacity of the tumor cells. Unexpectedly, sLeX was strongly down-regulated on tumor cell membranes in the course of heterophilic cell-cell contacts. The process occurred transiently, with a maximum effect 30-60 min after introducing tumor cells to the endothelial monolayer. Binding of tumor cells to immobilized E- and P-selectin IgG globulin chimeras was shown to be responsible for this phenomenon. CONCLUSION: A transient loss of sLeX is necessary for gastrointestinal tumor cells to invade endothelial cells. Due to the transient nature of the decrease in sLeX the controversy about the prognostic relevance of sLeX expression in colorectal and gastric cancer may be rooted in the stage of tumor invasion at the time of sLeX measurement.

Serum levels of basic fibroblast growth factor reflect disseminated disease in patients with testicular germ cell tumors.

The potential role of angiogenesis stimulators in the pathogenesis of different tumor entities has been confirmed in several studies. We measured the serum levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) in 51 patients with testicular germ cell tumors and in 39 healthy volunteers. Serum concentrations of bFGF, VEGF and PDGF-AB were determined by enzyme-linked immunosorbent assay. The median serum bFGF level for tumor patients was 3.46 pg/ml (range 0-61.6) compared to 0.7 pg/ml (0-11) in the control group (P<0.01). In patients with metastatic disease, the median serum bFGF level was 10.3 pg/ml (0-61.6) in contrast to 2.8 pg/ml (0-50) in patients with localized disease (P<0.01). The median serum VEGF and PDGF levels were 270 pg/ml (0-1,903) and 37,837 pg/ml (9,075-108,800), respectively, for tumor patients and 200 pg/ml (44-585) and 23,000 pg/ml (4,250-70,650) in the control group ( P<0.05). Our data suggest that angiogenesis, as reflected by serum concentrations of bFGF, VEGF and PDGF, plays a functional role in the growth and progression of testicular germ cell tumors.