De novo expression of the cell adhesion molecule E-selectin on gastric cancer endothelium.
OBJECTIVE
Angiogenesis and the molecular phenotype of the tumor vasculature determine tumor growth and metastasis.


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.
Mayer
B
B
Department of Surgery, Klinikum Grosshadern, University of Munich, Germany.
Spatz
H
H
Funke
I
I
Johnson
J P
JP
Schildberg
F W
FW
D002196:Capillaries / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D019040:E-Selectin / Q000235:genetics*; D004730:Endothelium, Vascular / Q000473:pathology*; D005753:Gastric Mucosa / Q000098:blood supply / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D007124:Immunoenzyme Techniques; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D019007:P-Selectin / Q000235:genetics; D011379:Prognosis; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
D019040:E-Selectin; D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1