De novo expression of the cell adhesion molecule E-selectin on gastric cancer endothelium

Abstract

Background and aims: Angiogenesis and the molecular phenotype of the tumor vasculature determine tumor growth and metastasis. Patients/Methods: In a series of 58 gastric cancer patients, vascular density and the antigenic profile of endothelial cells in normal, inflamed and malignant gastric tissues were compared using immunohistochemistry. Results: In both benign gastric mucosa and primary gastric cancer vascular density was inflammation-independent. However, increased vascularity in primary tumors was positively associated with a high tumor cell density suggesting tumor-induced angiogenesis (P=0.00001). P-selectin was expressed in most of the gastric mucosa samples on a small fraction of vessels and increased in the presence of moderate to strong leukocyte infiltrate. VCAM-1 positive mucosal vessels were rare and showed no association with inflammation. E-selectin and the EN 7/44 antigen defining budding vessels were absent on normal and inflamed endothelium. In contrast, in primary gastric cancer de novo expression of both E-selectin and the EN 7/44 antigen was observed. E-selectin positive vessels were preferentially found in vascular-rich tumor areas (P=0.0043) independently of leukocyte infiltration. Upregulation of VCAM-1 on tumor-associated endothelium was closely related to inflammation (P=0.019), while P-selectin expression resembled that in benign mucosa. Conclusions: Differentially expressed vascular molecules may influence the functional characteristics of extravasating leukocytes and represent new targets in anti-gastric cancer therapy.