| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Original Article |
Departments of Obstetrics and Gynecology (M.Z., F.H., S.K.-S., K.M., U.L.) and Biochemistry (K.T.P.), Justus Liebig University, D-35385 Giessen, Germany; Institute for Lasertechnologies, University of Ulm (K.K.-R.), D-89081 Ulm, Germany; and Department of Obstetrics and Gynecology, University of Louisville (C.V.R.), Louisville, Kentucky 40292
Address all correspondence and requests for reprints to: Dr. Marek Zygmunt, Department of Obstetrics and Gynecology, Justus Liebig University, Klinikstrasse 32, D-35385 Giessen, Germany. E-mail: marek.t. zygmunt{at}gyn.med.uni-giessen.de.
Abstract
Angiogenesis and vascular remodeling are crucial processes in tumor invasion and metastasis as well as in embryo implantation and normal development of the placenta. We have previously shown that hCG expressed in trophoblast and various malignant tumors promotes cellular motility and that uterine endothelium expresses hCG/LH receptor in vivo. In this study hCG was proposed to promote angiogenesis. A three-dimensional in vitro angiogenesis system consisting of uterine microvascular endothelial cells seeded on microcarriers and entrapped in a fibrin matrix was used to study the influence of hCG on neovascularization. Physiological concentrations of hCG (5–50,000 mU/ml) significantly increased in vitro capillary formation (up to 2.5-fold) and migration of endothelial cells in a Boyden chamber assay (up to 3.6-fold) in a dose-dependent manner, whereas hCG had no effect on cell proliferation. In vivo, hCG induced neovascularization in the chicken chorioallantoic membrane assay comparable to the activity of vascular endothelial growth factor. hCG-secreting tumors (choriocarcinoma, endometrium, and ovarian carcinoma) promoted in vitro neovascularization (up to 3-fold), whereas hCG-neutralizing antibody, pertussis toxin (G protein inhibitor), or GRGDTP peptide (integrin antagonist), respectively, abolished both tumor- and hCG-induced capillary sprout formation. Our data indicate a novel function for hCG in uterine adaptation to early pregnancy as well as in tumor development and underline the importance of hCG as an as yet unrecognized angiogenic factor.
This article has been cited by other articles:
 |
|
 |
|
  L Ranganath, W Taylor, L John, and Z Alfirevic Biochemical diagnosis of placental infarction/damage: acutely rising alkaline phosphatase Ann Clin Biochem, May 1, 2008; 45(3): 335 - 338. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Prast, L. Saleh, H. Husslein, S. Sonderegger, H. Helmer, and M. Knofler Human Chorionic Gonadotropin Stimulates Trophoblast Invasion through Extracellularly Regulated Kinase and AKT Signaling Endocrinology, March 1, 2008; 149(3): 979 - 987. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Rull, P. Hallast, L. Uuskula, J. Jackson, M. Punab, A. Salumets, R.K. Campbell, and M. Laan Fine-scale quantification of HCG beta gene transcription in human trophoblastic and non-malignant non-trophoblastic tissues Mol. Hum. Reprod., January 1, 2008; 14(1): 23 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Fluhr, S. Krenzer, G. M. Stein, B. Stork, M. Deperschmidt, D. Wallwiener, S. Wesselborg, M. Zygmunt, and P. Licht Interferon-{gamma} and tumor necrosis factor-{alpha} sensitize primarily resistant human endometrial stromal cells to Fas-mediated apoptosis J. Cell Sci., December 1, 2007; 120(23): 4126 - 4133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Herrmann-Lavoie, C. V. Rao, and A. Akoum Chorionic Gonadotropin Down-Regulates the Expression of the Decoy Inhibitory Interleukin 1 Receptor Type II in Human Endometrial Epithelial Cells Endocrinology, November 1, 2007; 148(11): 5377 - 5384. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Dos Santos, M.-N. Dieudonne, M.-C. Leneveu, R. Pecquery, V. Serazin, and Y. Giudicelli In vitro effects of chorionic gonadotropin hormone on human adipose development J. Endocrinol., August 1, 2007; 194(2): 313 - 325. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-H. Choi, A. S. T. Wong, H.-F. Huang, and P. C. K. Leung Gonadotropins and Ovarian Cancer Endocr. Rev., June 1, 2007; 28(4): 440 - 461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. C.K. Leung and J.-H. Choi Endocrine signaling in ovarian surface epithelium and cancer Hum. Reprod. Update, March 1, 2007; 13(2): 143 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Berndt, S. P. d'Hauterive, S. Blacher, C. Pequeux, S. Lorquet, C. Munaut, M. Applanat, M. A. Herve, N. Lamande, P. Corvol, et al. Angiogenic activity of human chorionic gonadotropin through LH receptor activation on endothelial and epithelial cells of the endometrium FASEB J, December 1, 2006; 20(14): 2630 - 2632. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Cameo, M. Szmidt, Z. Strakova, P. Mavrogianis, K. L. Sharpe-Timms, and A. T. Fazleabas Decidualization Regulates the Expression of the Endometrial Chorionic Gonadotropin Receptor in the Primate Biol Reprod, November 1, 2006; 75(5): 681 - 689. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-H. Choi, K.-C. Choi, N. Auersperg, and P. C.K. Leung Gonadotropins Activate Proteolysis and Increase Invasion through Protein Kinase A and Phosphatidylinositol 3-Kinase Pathways in Human Epithelial Ovarian Cancer Cells. Cancer Res., April 1, 2006; 66(7): 3912 - 3920. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. E. Murphy, R. Smith, W. B. Giles, and V. L. Clifton Endocrine Regulation of Human Fetal Growth: The Role of the Mother, Placenta, and Fetus Endocr. Rev., April 1, 2006; 27(2): 141 - 169. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. D. Baird, J. S. Kesner, and D. B. Dunson Luteinizing Hormone in Premenopausal Women May Stimulate Uterine Leiomyomata Development Reproductive Sciences, February 1, 2006; 13(2): 130 - 135. [Abstract] [PDF]
|
|
|
|
 |
|
 K. Rull and M. Laan Expression of {beta}-subunit of HCG genes during normal and failed pregnancy Hum. Reprod., December 1, 2005; 20(12): 3360 - 3368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T R. Kumar What have we learned about gonadotropin function from gonadotropin subunit and receptor knockout mice? Reproduction, September 1, 2005; 130(3): 293 - 302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-H. Choi, K.-C. Choi, N. Auersperg, and P. C K Leung Gonadotropins upregulate the epidermal growth factor receptor through activation of mitogen-activated protein kinases and phosphatidyl-inositol-3-kinase in human ovarian surface epithelial cells Endocr. Relat. Cancer, June 1, 2005; 12(2): 407 - 421. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Akoum, C. N. Metz, and M. Morin Marked Increase in Macrophage Migration Inhibitory Factor Synthesis and Secretion in Human Endometrial Cells in Response to Human Chorionic Gonadotropin Hormone J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2904 - 2910. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zygmunt, T. McKinnon, F. Herr, P.K. Lala, and V.K. M. Han HCG increases trophoblast migration in vitro via the insulin-like growth factor-II/mannose-6 phosphate receptor Mol. Hum. Reprod., April 1, 2005; 11(4): 261 - 267. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Fields and M. Shemesh Extragonadal Luteinizing Hormone Receptors in the Reproductive Tract of Domestic Animals Biol Reprod, November 1, 2004; 71(5): 1412 - 1418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Knofler, L. Saleh, S. Bauer, B. Galos, H. Rotheneder, P. Husslein, and H. Helmer Transcriptional Regulation of the Human Chorionic Gonadotropin {beta} Gene during Villous Trophoblast Differentiation Endocrinology, April 1, 2004; 145(4): 1685 - 1694. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. D. Liang, T. Korff, J. Eckhardt, J. Rifaat, N. Baal, F. Herr, K. T. Preissner, and M. Zygmunt Oncodevelopmental {alpha}-Fetoprotein Acts as a Selective Proangiogenic Factor on Endothelial Cell from the Fetomaternal Unit J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1415 - 1422. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Bartha, R. Romero-Carmona, M. Escobar-Llompart, O. Paloma-Castro, and R. Comino-Delgado Human Chorionic Gonadotropin and Vascular Endothelial Growth Factor in Normal and Complicated Pregnancies Obstet. Gynecol., November 1, 2003; 102(5): 995 - 999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Herr, O. D. Liang, J. Herrero, U. Lang, K. T. Preissner, V. K. M. Han, and M. Zygmunt Possible Angiogenic Roles of Insulin-Like Growth Factor II and Its Receptors in Uterine Vascular Adaptation to Pregnancy J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4811 - 4817. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Dabizzi, I. Noci, P. Borri, E. Borrani, M. Giachi, M. Balzi, G. L. Taddei, M. Marchionni, G. F. Scarselli, and A. Arcangeli Luteinizing Hormone Increases Human Endometrial Cancer Cells Invasiveness through Activation of Protein Kinase A Cancer Res., July 15, 2003; 63(14): 4281 - 4286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Lin, X. Li, Z. M. Lei, and Ch. V. Rao Human Cervix Contains Functional Luteinizing Hormone/Human Chorionic Gonadotropin Receptors J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3409 - 3414. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Y. Liu, A. K. Death, and D. J. Handelsman Androgens and Cardiovascular Disease Endocr. Rev., June 1, 2003; 24(3): 313 - 340. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
