PURPOSE: Expression of the adhesion molecule L1-CAM (L1) has been shown to correlate with early recurrence in breast cancer. Here, we investigated whether L1-CAM expression of breast cancer cells might influence adherence to human pulmonary microvascular endothelial cells (HPMEC) and thus promote metastasis. METHODS: MDA-MB231-Fra2 breast cancer cells that express high levels of L1-CAM (L1(high) cells) were stably transfected to generate clones with strong L1-CAM downregulation. Adhesion to activated HPMEC was studied in dynamic cell flow and static assays. Potential binding partners on endothelial cells were identified by blocking experiments and adhesion assays after coating of the flow channels with recombinant proteins. RESULTS: Adhesion of L1(high) cells to activated HPMEC was significantly higher compared to L1l(ow) clones under flow conditions. Blocking experiments and adhesion assays with recombinant proteins identified activated leucocyte cell adhesion molecule (ALCAM) or L1 itself, but not ICAM-1, as potential binding partners on endothelial cells. E-selectin blocking antibodies strongly diminished the adherence of breast cancer cells irrespective of their L1-CAM expression. CONCLUSIONS: Our experiments indicate that L1-CAM expression on breast cancer cells can promote adherence to activated endothelial cells by binding to endothelial L1-CAM or ALCAM. This mechanism might lead to increased metastasis and a poor prognosis in L1-CAM-positive carcinomas in vivo. Therefore, L1-CAM might be a suitable therapeutic target in breast cancers with a high L1-CAM expression.
PURPOSE: Expression of the adhesion molecule L1-CAM (L1) has been shown to correlate with early recurrence in breast cancer. Here, we investigated whether L1-CAM expression of breast cancer cells might influence adherence to human pulmonary microvascular endothelial cells (HPMEC) and thus promote metastasis. METHODS: MDA-MB231-Fra2 breast cancer cells that express high levels of L1-CAM (L1(high) cells) were stably transfected to generate clones with strong L1-CAM downregulation. Adhesion to activated HPMEC was studied in dynamic cell flow and static assays. Potential binding partners on endothelial cells were identified by blocking experiments and adhesion assays after coating of the flow channels with recombinant proteins. RESULTS: Adhesion of L1(high) cells to activated HPMEC was significantly higher compared to L1l(ow) clones under flow conditions. Blocking experiments and adhesion assays with recombinant proteins identified activated leucocyte cell adhesion molecule (ALCAM) or L1 itself, but not ICAM-1, as potential binding partners on endothelial cells. E-selectin blocking antibodies strongly diminished the adherence of breast cancer cells irrespective of their L1-CAM expression. CONCLUSIONS: Our experiments indicate that L1-CAM expression on breast cancer cells can promote adherence to activated endothelial cells by binding to endothelial L1-CAM or ALCAM. This mechanism might lead to increased metastasis and a poor prognosis in L1-CAM-positive carcinomas in vivo. Therefore, L1-CAM might be a suitable therapeutic target in breast cancers with a high L1-CAM expression.
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