Morphine Attenuates Endothelial Cell Adhesion Molecules Induced by the Supernatant of LPS-Stimulated Colon Cancer Cells

Abstract

A large reservoir of bacterial lipopolysaccharide (LPS) is available in the colon and this could promote colon cancer metastasis by enhancing tumor cell adhesion, intravasation, and extravasation. Furthermore, adhesion molecules like ICAM-1, VCAM-1, and E-selectin play important roles in the adhesion of tumor cells to endothelium. This study was designed to determine whether morphine can attenuate the expressions of adhesion molecules up-regulated by the supernatant of LPS-stimulated HCT 116 colon cancer cells (LPS-Sup). In this study, we divided to three groups by cell-growth medium of human umbilical vascular endothelial cells (HUVECs): the control group was incubated in growth factor-free endothelial medium, the Sup group was incubated in the supernatant of HCT 116 cells (Sup), and the LPS-Sup group was incubated in LPS-Sup. To observe effect of morphine to the adhesion molecules expressions in the LPS-Sup group, we co-treated morphine with LPS or added it to LPS-Sup. Adhesion molecule expressions on HUVECs in all three groups were measured during incubation period. Consquentially, ICAM-1, VCAM-1, and E-selectin expressions on HUVECs were significantly lower when morphine was co-treated with LPS than not co-treated. Thus, we suggest that morphine affects the expressions of adhesion molecules primarily by attenuating LPS stimuli on tumor cells.

Mu Opioid Receptor 1 (MOR-1) Expression in Colorectal Cancer and Oncological Long-Term Outcomes: A Five-Year Retrospective Longitudinal Cohort Study

“…Preclinical investigations appear to indicate that the role of MOR-1 agonists is cell type-, dose-and time-dependent. Morphine has been found to be a suppressor of cells metastatic behavior [33], inhibitor adhesion molecules (ICAM-1) expression in endothelial cells [34]. Moreover, chronic administration of morphine inhibited tumorigenesis and metastasis [35] and reduced liver metastasis in animals [36].…”

The Ubiquitin–CXCR4 Axis Plays an Important Role in Acute Lung Infection–Enhanced Lung Tumor Metastasis

“…The effects of LPS in cancer cells may then affect host cells. For example, the secreted factor(s) from LPS-stimulated colon cancer cells enhances endothelial cell adhesion (48). However, our data collectively suggest that the effects shown here were not due to a direct action of LPS, but rather its ability to alter the lung microenvironment, making it a more suitable and attractive “niche” for tumor cell spreading and colonization.…”

Vascular cell adhesion molecule‐1 (VCAM‐1)—An increasing insight into its role in tumorigenicity and metastasis

“…Hence, several drugs with miscellaneous indications exhibit anti‐adhesive effects on TCs due to a downregulation of VCAM‐1 and other CAMs on endothelial cells. Morphine demonstrated to decrease VCAM‐1 expression on HUVECs treated with the supernatant of LPS stimulated colon cancer cells . Resveratrol prevented hepatic melanoma metastasis by attenuation of IL‐18 dependent expression of VCAM‐1 on sinusoidal endothelial cells, and Simvastatin induced a VCAM‐1 downregulation on peritoneal mesothelial cells .…”

“…Morphine demonstrated to decrease VCAM-1 expression on HUVECs treated with the supernatant of LPS stimulated colon cancer cells. 158 Resveratrol prevented hepatic melanoma metastasis by attenuation of IL-18 dependent expression of VCAM-1 on sinusoidal endothelial cells, 159 and Simvastatin induced a VCAM-1 downregulation on peritoneal mesothelial cells. 160 Others identified further potential target molecules responsible for an upregulation of VCAM-1 contributing to cancer metastasis e.g.…”