Tumor necrosis factor and epidermal growth factor modulate migration of human microvascular endothelial cells and production of tissue-type plasminogen activator and its inhibitor

Direct inhibition of EGF receptor activation in vascular endothelial cells by gefitinib (‘Iressa’, ZD1839)

“…14) Both indirect and direct mechanisms have been considered to underlie EGF/TGFα-induced angiogenesis: on the one hand, EGF/TGFα secreted by tumor cells and/or tumor stoma cells enhanced the production of potent angiogenic factors, such as VEGF, IL-8, and metalloproteinases, resulting in angiogenesis via the paracrine and/or autocrine route [31][32][33] ; on the other hand, activation of EGFR expressed in neo-vasculature in response to EGF/TGFα induced an angiogenic switch of the endothelial cells. 18,20,22) Concerning the latter direct mechanism, some dividing endothelial cells have been shown to express EGFR. 21,23,34) In addition, Fidler and colleagues have recently reported that tumor-associated endothelial cells express activated EGFR, and also that administration of EGFR tyrosine kinase inhibitors decreases this EGFR activation, with concomitant inhibition of tumor growth and/or metastasis and induction of apoptosis of the endothelial cells.…”

“…We have reported that EGF/TGFα-induced angiogenesis might be attributable to its signaling through direct interaction with vascular endothelial cells, 14,18) and also to angiogenesis-related factors that are produced from cancer cells and vascular endothelial cells, based on studies using various angiogenesis models. 14,19,20) However, it remains unclear whether EGF-induced angiogenesis in vivo is mediated by direct interaction with endothelial cells. The vascular endothelial cells in a number of tumor types are known to express EGFR, [21][22][23] and suppression of VEGF or EGF expression inhibited the growth of a wide variety of tumor types in a murine tumor model, while angiogenesis inhibitors that target VEGF receptor or EGFR reduced tumor growth, metastasis, and the microvessel density of human pancreatic cancer in nude mice.…”

Involvement of wound-associated factors in rat brain astrocyte migratory response to axonal injury: in vitro simulation.

“…Among these are growth factors, such as epidermal growth factor (EGF), heparin-binding EGF (HB-EGF), transforming growth factor-␣ (TGF-␣ ), transforming growth factor-␤ 1 (TGF-␤ 1 ), insulin-like growth factor-1 (IGF-1), and basic fibroblast growth factor (bFGF), in tissue repair and wound healing (11)(12)(13)(14)(15). Some of these factors are angiogenic (16), some bind to ECM components (17-21), and some affect cell migration in various model systems in vitro (22)(23)(24)(25)(26)(27). Likely candidates of such components are those which have been shown to be involved in tissue repair and wound healing.…”

Induction of vascular endothelial tubular morphogenesis by human glioma cells. A model system for tumor angiogenesis.

“…Both EGF and TGF-a have been shown to be angiogenic factors (6,7). In human omental microvascular endothelial cells in culture, EGF or TGF-a has been identified as the most potent growth factor in stimulating cell migration, synthesis of tissue type plasminogen activator (PA), and tube formation in collagen-containing gels (8)(9)(10)(11)(12)(13). Other angiogenic factors are acidic FGF and bFGF, which have a high affinity for heparin ( 14,15).…”