Involvement of tumor necrosis factor α and very late activation antigen 4/vascular cell adhesion molecule 1 interaction in surgical-stress-enhanced experimental metastasis |
| |
Authors: | A Higashiyama Hideaki Watanabe K Okumura Hideo Yagita |
| |
Institution: | (1) The First Department of Surgery, School of Medicine, Juntendo University, Building 5, Room 213, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113, Japan, JP;(2) Department of Immunology, School of Medicine, Juntendo University, Tokyo, Japan, JP |
| |
Abstract: | We examined the influence of surgical stress on hematogenous metastasis of malignant tumor cells. The study was performed
by focusing on the involvement of inflammatory cytokines in the serum, raised acutely after surgery, and endothelial adhesion
molecules in the metastatic process. Surgical stress, given to C57BL/6 mice before B16-BL6 melanoma inoculation, significantly
enhanced the pulmonary metastasis. This enhancement was seen when the surgery lasted for more than 2 h. After the 2-h surgery,
the enhancement of pulmonary metastasis was seen most remarkably when B16-BL6 was inoculated 24 h after surgery. The serum
level of tumor necrosis factor α (TNFα) in the mice that underwent the 2-h surgery peaked 12 h after the surgery. In contrast,
serum interferon γ was not detectable. Administration of an anti-TNFα mAb before the surgery inhibited the enhanced metastasis
by inhibiting the increased expression of vascular cell adhesion molecule 1 (VCAM-1) on lung vascular endothelium after the
surgery. Pretreatment of B16-BL6 cells with an anti-very late activation antigen 4 (anti-VLA-4) mAb completely inhibited the
enhanced metastasis after surgery. Administration of an anti-VCAM-1 mAb before surgery also inhibited the enhancement. These
results indicate that serum TNFα , raised by surgical stress, is critically involved in the enhanced pulmonary metastasis
of mouse melanoma by inducing VCAM-1 expression on lung vascular endothelium.
Received: 22 January 1996 / Accepted: 1 April 1996 |
| |
Keywords: | Surgical stress Pulmonary metastasis TNF-α VLA-4 VCAM-1 |
本文献已被 SpringerLink 等数据库收录! |
|