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Induction of Proteases in Peritoneal Carcinomatosis, the Role of ICAM-1/CD43 Interaction.

Title: Induction of Proteases in Peritoneal Carcinomatosis, the Role of ICAM-1/CD43 Interaction.
Authors: Alkhamesi, NA
Roberts, G
Ziprin, P
Peck, DH
Item Type: Journal Article
Abstract:  INTRODUCTION: The development of peritoneal metastases is a significant clinical issue in the treatment of abdominal cancers and is associated with poor prognosis. We have previously shown that ICAM-1-CD43 interaction plays a significant role in tumor adhesion. However, an invasive phenotype is critical to establish tumor progression via cell associated and secreted proteases including matrix metalloproteinases. High metalloproteinases level significantly enhanced metastasis phenotype on tumors, a detrimental effect on surgical outcome. We investigated the role of direct and indirect signaling between the mesothelium and the tumor cells in enhancing tumor invasion and possible therapeutic intervention. METHODS: Mesothelial cells were enzymatically derived from human omental tissue and implanted in 24 wells plates. Colorectal cancer cells were then introduced and allowed a direct and an indirect contact with the mesothelial layer. Anti-ICAM antibodies, anti-CD43 antibodies, and heparin were used to block MMP production. Gelatin zymography was performed on the supernatant to detect MMPs activity. RESULTS: MMP production was observed in mesothelial and tumor cells. Direct contact between cell types enhanced MMP9 and 2 (p < 0.05). Indirect contact also stimulate MMPs but at a lower degree. ICAM-1 blocking antibodies attenuated MMP production in direct contact to that observed in the indirect. Heparin introduction achieved a similar outcome. CONCLUSIONS: ICAM-1-CD43 interaction plays a vital role in tumor cells-peritoneum adhesion and invasion, which is manifested by the increased production of MMPs leading to tumor invasion and peritoneal loco-regional. Blocking this interaction with heparin can provide a new therapeutic option.
Issue Date: 31-Jan-2007
URI: http://hdl.handle.net/10044/1/21965
ISSN: 1177-2719
Publisher: Libertas Academica
Start Page: 377
End Page: 384
Journal / Book Title: Biomark Insights
Volume: 2
Copyright Statement: © 2007 The Authors. Copyright in this article, its metadata, and any supplementary data is held by its author or authors. It is published under the Creative Commons Attribution By licence. For further information go to: http://creativecommons.org/licenses/by/3.0/
Appears in Collections:Department of Surgery and Cancer

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