During angiogenesis, vascular endothelial growth factor regulate natural killer cell adhesion to tumor endothelium

Abstract

Localization of activated natural killer (A-NK) cells in the microvasculature of growing tumors is the result of recognition of the intracellular and vascular cell-adhesion molecules ICAM-1 and VCAM-1 on the tumor endothelium, mediated by lymphocyte function-associated protein LFA-1 and vascular lymphocyte function-associated protein VLA-4. In vitro and in vivo studies of A-NK cell adhesion to endothelial cells showed that vascular endothelial growth factor (VEGF) promotes adhesion, whereas basic fibroblast growth factor (bFGF) inhibits adhesion through the regulation of these molecules on tumor vasculature. Thus, some angiogenic factors may facilitate lymphocyte recognition of angiogenic vessels, whereas others may provide such vessels with a mechanism that protects them from cytotoxic lymphocytes.

In oesophageal squamous cell carcinoma vascular endothelial growth factor is associated with p53 mutation, advanced stage and poor prognosis

“…It may also increase the numbers of lymphatic-haematogenous communications, allowing more intravascular micrometastasis to enter the lymphatic spaces (Blood et al, 1990). VEGF is also known as vascular permeability factor and is thought to activate natural killer cells into connecting with endothelial cells through adhesional molecules (Melder et al, 1996). Furthermore, VEGF has been shown to induce urokinase-type plasminogen activator (uPA), tissue-type PA (tPA) and plasminogen activator inhibitor-I (PAl-1) in vascular endothelial cells and bovine lymphatic endothelial cells (Pepper et al, 1991(Pepper et al, , 1994.…”

Vascular Endothelial Growth Factor (VEGF)-Induced Retinal Vascular Permeability Is Mediated by Intercellular Adhesion Molecule-1 (ICAM-1)

“…Finally, these findings are consistent with our work showing VEGF-induced ICAM-1 expression in the retinal vasculature. 8 Leukocyte adhesion secondary to VEGF has been previously demonstrated in the microvasculature of growing tumors, 18 the corneas of rabbits, 19 and the skin of transgenic mice. 20 Detmar and associates expressed VEGF using the keratin 14 promoter and observed the induction of a vascular cell adhesion molecule-1 (VCAM-1)-mediated leukostasis in the dermis.…”

“…20 In a separate study, Melder and associates demonstrated VEGF-induced leukocyte adhesion to tumor vasculature via ICAM-1 and VCAM-1. 18 A tissue-specific heterogeneity for the mediating adhesion molecules may exist, as the Detmar study showed that ICAM-1 inhibition did not affect VEGF-induced skin leukostasis. 18 The present data extend these observations by suggesting that VEGF-induced leukostasis is not an epiphenomenon, as the process is linked to capillary nonperfusion and increased vascular permeability.…”

Thymidine phosphorylase expression in normal, hyperplastic and neoplastic prostates: correlation with tumour associated macrophages, infiltrating lymphocytes, and angiogenesis

“…Certainly, this would explain our finding that extensive lymphocytic infiltration of the prostatic tumour stroma is related with strong TP expression by cancer and stromal cells. The pathway by which lymphocytes, or specific subpopulations of lymphocytes, trigger the expression of TP is not clear, although there are reports implicating CD4 positive cells in tumour angiogenesis (Blotnick et al, 1994) and natural killer (NK) cells in complex interactions with angiogenic factors (Melder et al, 1996). Furthermore, a direct association between lymphocytic and macrophage stromal infiltration was noted.…”