Lipopolysaccharide induces the interactions of breast cancer and endothelial cells via activated monocytes.

The adhesion of circulating cancer cells to vascular endothelium is a key step in hematogenous metastasis. Cancer cell-endothelium interactions are mediated by cell adhesion molecules that can also be involved in the arrest of monocytes and other circulating leukocytes on endothelium in inflammation. Static and microfluidic flow adhesion assays as well as flow cytometry were conducted in this study to elucidate the role of monocytes, bacterial lipopolysaccharide (LPS), and histamine in breast cancer cell adhesion to vascular endothelial cells. Tumor necrosis factor-α (TNF-α) released from LPS-treated monocytes triggered the expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells. Histamine augmented the TNF-α effect, leading to a high number of arrested breast cancer cells under both static and shear flow conditions. LPS-treated monocytes were shown to enhance the arrest of breast cancer cells by anchoring the cancer cells to activated endothelial cells. This anchorage was achieved by binding cancer cell ICAM-1 to monocyte β2 integrins and binding endothelial ICAM-1 and VCAM-1 to monocyte β1 and β2 integrins. The results of this study imply that LPS is an important risk factor for cancer metastasis and that the elevated serum level of histamine further increases the risk of LPS-induced cancer metastasis. Preventing bacterial infections is essential in cancer treatment, and it is particularly vital for cancer patients affected by allergy.