The effect of epidermal growth factor on vascular endothelial growth factor secretion by endometrial stromal cells

Abstract

Endometrial stromal cells undergo morphological and functional changes to facilitate oocyte implantation under regulation of various hormones and growth factors. We studied physiological induction by epidermal growth factor (EGF) of vascular endothelial growth factor (VEGF) in these cells. In human endometrial stromal cells, the effect of EGF, genistein, tryphostin AG1478 (a tyrosine kinase inhibitor), and wortmannin (a phosphatidylinositol 3-kinase inhibitor) on production of VEGF was examined. Total RNA was extracted and VEGF mRNA expression was quantified by Northern analysis. EGF induced production of VEGF by stromal cells in a time-dependent manner; the effect became significant after 12 h and increased further between 24 and 48 h (P<0.05). Dose dependency was also significant (P<0.01). Genistein, tryphostin AG1478, and wortmannin partially suppressed the increase in production induced by EGF (P<0.01, P<0.01, P<0.01), respectively. Production of EGF by fertilized oocytes and trophoblasts has been reported in early pregnancy. VEGF is believed to be induced by EGF through mechanisms involving tyrosine kinase and phosphatidylinositol 3-kinase. The increase in VEGF may contribute to neovascularization that promotes proliferation of endometrium and placentation.

Thyrotropin (TSH)-Induced Production of Vascular Endothelial Growth Factor in Thyroid Cancer Cellsin Vitro: Evaluation of TSH Signal Transduction and of Angiogenesis-Stimulating Growth Factors

“…EGF has been shown to increase VEGF production in human endometrial stromal cells (14). Involvement of EGF in the angiogenetic cascade was also suggested by the ability of EGF to induce thrombospondin-1 and plasminogen activator inhibitor-1 (53).…”

“…That these factors may also modulate VEGF production is suggested by circumstantial evidence. For instance, it has recently been reported that VEGF secretion increased upon stimulation of primary cultures of papillary thyroid carcinoma as well as cell lines of leiomyosarcoma and breast cancer with hepatocyte growth factor (HGF), and that epidermal growth factor (EGF) induced VEGF production in human endometrial cells (12)(13)(14). In addition, TGF-␤ has been associated with VEGF expression and microvessel density in colorectal cancer (15).…”

The effect of insulin-like growth factor-I on production of vascular endothelial growth factor by amnion-derived (WISH) cells

“…These findings suggest that the production of VEGF may be regulated by other mechanism involving via tyrosine kinase with IGF-I receptor to PI 3-kinase. We have previously reported that VEGF is regulated involving PI 3-kinase in human endometrium [21]. We demonstrated that PI 3-kinase might be another important pathway to modulate the production of VEGF in the amnion.…”

“…Recent studies have demonstrated the production of VEGF by several organs of the reproductive system including the ovaries [17], endometrium of the uterus [18][19][20][21], and placenta [15,22]. VEGF is expressed in the trophoblast throughout pregnancy, as has been verified by immunohistochemical study [23][24][25].…”

The production of vascular endothelial growth factor and metalloproteinase via protease-activated receptor in human endometrial stromal cells

“…Recent studies have demonstrated the production of VEGF by several organs in the reproductive system, including the ovaries (29), endometrium of the uterus (27,28,30,31), and placenta (7,32,33). Female reproductive tissues, especially the endometria of menstruating primates, show an exceptional degree of angiogenesis accompanying the monthly cycle.…”