A potential transforming growth factor α/epidermal growth factor receptor autocrine circuit in placental cytotrophoblasts

• Published in: Cell growth & differentiation Vol. 4; no. 5; pp. 387 - 393
• Main Authors: FILLA, M. S, CHEN XUE ZHANG, KAUL, K. L
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-05-1993
• Subjects: Biological and medical sciences; Cells, Cultured; Culture Media, Serum-Free; Embryology: invertebrates and vertebrates. Teratology; Enzyme-Linked Immunosorbent Assay; Female; Fetal membranes; Fundamental and applied biological sciences. Psychology; General aspects. Development. Fetal membranes; Humans; Immunoenzyme Techniques; Placental Hormones - physiology; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Receptor, Epidermal Growth Factor - analysis; Receptor, Epidermal Growth Factor - physiology; Thymidine - metabolism; Transforming Growth Factor alpha - analysis; Transforming Growth Factor alpha - biosynthesis; Trophoblasts - metabolism; Trophoblasts - physiology; Human; Cell proliferation; Epidermal growth factor; Placenta; Fetal membrane; Transforming growth factor; Stimulation; Biological receptor
• ISSN: 1044-9523; 2377-0732

A potential autocrine loop involving transforming growth factor alpha (TGF-alpha) and the epidermal growth factor (EGF) receptor (EGFR) in benign placental cytotrophoblasts was examined. EGFR were localized to villous cytotrophoblasts and syncytiotrophoblasts in frozen sections throughout gestation using immunoperoxidase (IP) and autoradiography with 125I-EGF. EGF and TGF-alpha stimulated uptake of [3H]-thymidine in cultured cytotrophoblasts from first and second trimester placentae, demonstrating both functional EGFR and the mitogenic ability of either growth factor in these cells. Using IP, TGF-alpha was localized consistently throughout gestation to cytotrophoblasts with little or no staining of syncytiotrophoblasts in formalin-fixed sections. Variable staining of villous stromal cells and intense staining of maternal decidua were also observed. TGF-alpha production by cultured cytotrophoblasts was confirmed in vitro via IP analysis of cytotrophoblasts cultured in serum-free media and enzyme-linked immunosorbent assay analysis of cytotrophoblast serum-free conditioned media. The results suggest that a TGF-alpha/EGFR autocrine loop stimulates proliferation of benign cytotrophoblasts.