Anti-metastatic effect of methylprednisolone targeting vascular endothelial cells under surgical stress
Takaomi Hagi1, Yukinori Kurokawa2, Noboru Kobayashi1
1Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Abstract:
Perioperative systemic inflammation induced by surgical stress elevates the risk of hematogenous cancer metastasis. This study investigated the anti-metastatic effects and mechanisms of methylprednisolone (MP) administration for surgical stress. We examined the effects of MP on the expression of adhesion molecules in human vascular endothelial cells and in a murine hepatic metastasis model under lipopolysaccharide (LPS) administration, which mimics systemic inflammation induced by surgical stress. Serum E-selectin level was measured in blood samples obtained from 32 gastric cancer patients who were randomly assigned to treat preoperatively with or without MP. The expression of E-selectin in LPS-induced vascular endothelial cells was suppressed by MP. An adhesion assay showed the number of LPS-induced adherent tumour cells was significantly lower following MP. In the in vivo study, LPS significantly elevated the number of hepatic metastases, but pretreatment with MP before LPS significantly inhibited this elevation. The LPS-induced expression of E-selectin in the vascular endothelium of the portal vein was suppressed by MP. In human clinical samples, serum E-selectin level was significantly decreased by preoperative MP. Suppression of surgically induced systemic inflammation by MP administration might prevent hematogenous cancer metastases by suppressing the induction of E-selectin expression in the vascular endothelium.
Insights
Methylprednisolone (MP) reduces cancer metastasis by suppressing inflammation. This study found MP lowers E-selectin, a key molecule in cancer cell adhesion, in both lab models and cancer patients, highlighting its anti-metastatic potential.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Perioperative systemic inflammation, triggered by surgical stress, increases the risk of hematogenous cancer metastasis.
- Understanding the mechanisms linking inflammation and metastasis is crucial for developing effective anti-cancer strategies.
Purpose of the Study:
- To investigate the anti-metastatic effects of methylprednisolone (MP) in the context of surgical stress-induced inflammation.
- To elucidate the underlying mechanisms of MP's action, focusing on adhesion molecule expression.
Main Methods:
- Examined MP's effect on E-selectin expression in human vascular endothelial cells stimulated with lipopolysaccharide (LPS).
- Assessed tumor cell adhesion to endothelial cells in vitro.
- Evaluated MP's efficacy in a murine hepatic metastasis model under LPS administration.
- Measured serum E-selectin levels in gastric cancer patients receiving preoperative MP.
Main Results:
- MP suppressed LPS-induced E-selectin expression in endothelial cells and reduced tumor cell adhesion.
- In vivo, MP pretreatment significantly inhibited LPS-induced hepatic metastasis.
- MP administration decreased serum E-selectin levels in gastric cancer patients.
Conclusions:
- Methylprednisolone (MP) administration suppresses surgically induced systemic inflammation.
- MP may prevent hematogenous cancer metastasis by inhibiting E-selectin expression in vascular endothelium.
- MP shows potential as an adjunctive therapy to reduce cancer metastasis risk.
