Human Reproduction, Vol. 16, No. 5, 836-845,
May 2001
© 2001 European Society of Human Reproduction and Embryology
Endometrial stromal cells regulate epithelial cell growth in vitro: a new co-culture model
1 Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, 2 Departments of Laboratory Pathology and Medicine, University of North Carolina, Chapel Hill, NC, USA, 3 Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Finland and 4 Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, NC, USA
The regulation of epithelial cell function and morphogenesis by the paracrine effectors from the mesenchyme or stroma has been well established using in-vivo studies. A more complete understanding of these relationships has been delayed due, in part, to a lack of appropriate co-culture models. In this study, we describe a co-culture model which demonstrates that normal paracrine relationships can be reconstituted in vitro and that human endometrial stromal cells regulate both growth and differentiation of primary human endometrial epithelial cells. Interesting differences in the proliferation of stromal and epithelial cells were noted in response to the basement membrane extract, Matrigel®. Exposure of stromal cells to Matrigel® enhanced the paracrine capacity of these cells in vitro. When epithelial cells were co-cultured in contact with stromal cells embedded in Matrigel®, epithelial cell growth was inhibited by 65–80% compared to controls. Stromal cells in contact with Matrigel® also regulated epithelial cell differentiation, as shown by induction of glycodelin expression. These co-culture studies show great promise as a method to investigate the cellular interactions between endometrial stromal and epithelial cells and their environment and to understand the molecular basis for the regulation of normal growth and differentiation of cells within complex tissues such as the endometrium.
Key words: co-culture/endometrium/epithelium/glycodelin/stroma
5 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, CB # 7570 MacNidere Building, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599–7570, USA. E-mail: lessey{at}med.unc.edu
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Zhang, M. Li, X. Zheng, Y. Sun, Z. Wen, and X. Zhao Endometriotic stromal cells lose the ability to regulate cell-survival signaling in endometrial epithelial cells in vitro Mol. Hum. Reprod., October 1, 2009; 15(10): 653 - 663. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Polotsky, L. Zhu, N. Santoro, and J. W. Pollard Lithium chloride treatment induces epithelial cell proliferation in xenografted human endometrium Hum. Reprod., August 1, 2009; 24(8): 1960 - 1967. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. S. Carmon and D. S. Loose Secreted Frizzled-Related Protein 4 Regulates Two Wnt7a Signaling Pathways and Inhibits Proliferation in Endometrial Cancer Cells Mol. Cancer Res., June 1, 2008; 6(6): 1017 - 1028. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Barbier, H. J. Kloosterboer, and D. G. Kaufman Effects of Tibolone Metabolites on Human Endometrial Cell Lines in Co-culture Reproductive Sciences, January 1, 2008; 15(1): 75 - 82. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Iwase, H. Ando, T. Nagasaka, M. Goto, T. Harata, and F. Kikkawa Distribution of Endothelin-converting Enzyme-1 and Neutral Endopeptidase in Human Endometrium J. Histochem. Cytochem., December 1, 2007; 55(12): 1229 - 1235. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. A. Adissu, E. K. Asem, and S. A. Lelievre Three-Dimensional Cell Culture to Model Epithelia in the Female Reproductive System Reproductive Sciences, December 1, 2007; 14(8_suppl): 11 - 19. [Abstract] [PDF]
|
|
|
|
|
|
P.G.L. Lalitkumar, S. Lalitkumar, C.X. Meng, A. Stavreus-Evers, F. Hambiliki, U. Bentin-Ley, and K. Gemzell-Danielsson Mifepristone, but not levonorgestrel, inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum. Reprod., November 1, 2007; 22(11): 3031 - 3037. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Iwase, H. Ando, T. Nagasaka, D. Shibata, T. Harata, Y. Shimomura, M. Goto, and F. Kikkawa Neutral Endopeptidase Expressed by Decidualized Stromal Cells Suppresses Akt Phosphorylation and Deoxyribonucleic Acid Synthesis Induced by Endothelin-1 in Human Endometrium Endocrinology, November 1, 2006; 147(11): 5153 - 5159. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Welsh, P. T. K. Saunders, N. I. Marchetti, and R. M. Sharpe Androgen-Dependent Mechanisms of Wolffian Duct Development and Their Perturbation by Flutamide Endocrinology, October 1, 2006; 147(10): 4820 - 4830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Chapdelaine, J. Kang, S. Boucher-Kovalik, N. Caron, J. P. Tremblay, and M. A. Fortier Decidualization and maintenance of a functional prostaglandin system in human endometrial cell lines following transformation with SV40 large T antigen Mol. Hum. Reprod., May 1, 2006; 12(5): 309 - 319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-L. Shi, X.-Z. Luo, X.-Y. Zhu, K.-Q. Hua, Y. Zhu, and D.-J. Li Effects of combined 17beta-estradiol with TCDD on secretion of chemokine IL-8 and expression of its receptor CXCR1 in endometriotic focus-associated cells in co-culture Hum. Reprod., April 1, 2006; 21(4): 870 - 879. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Barbier, K. A. Becker, M. A. Troester, and D. G. Kaufman Expression of Exogenous Human Telomerase in Cultures of Endometrial Stromal Cells Does Not Alter Their Hormone Responsiveness Biol Reprod, July 1, 2005; 73(1): 106 - 114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Hombach-Klonisch, A Kehlen, P A Fowler, B Huppertz, J F Jugert, G Bischoff, E Schluter, J Buchmann, and T Klonisch Regulation of functional steroid receptors and ligand-induced responses in telomerase-immortalized human endometrial epithelial cells J. Mol. Endocrinol., April 1, 2005; 34(2): 517 - 534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Blauer, P.K. Heinonen, P.M. Martikainen, E. Tomas, and T. Ylikomi A novel organotypic culture model for normal human endometrium: regulation of epithelial cell proliferation by estradiol and medroxyprogesterone acetate Hum. Reprod., April 1, 2005; 20(4): 864 - 871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I.-S. Hong, S.-H. Kim, M. K. Koong, J. H. Jun, S.-H. Kim, Y.-S. Lee, and K.-S. Kang Roles of p38 and c-jun in the differentiation, proliferation and immortalization of normal human endometrial cells Hum. Reprod., October 1, 2004; 19(10): 2192 - 2199. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Jakubowicz, P. A. Essah, M. Seppala, S. Jakubowicz, J.-P. Baillargeon, R. Koistinen, and J. E. Nestler Reduced Serum Glycodelin and Insulin-Like Growth Factor-Binding Protein-1 in Women with Polycystic Ovary Syndrome during First Trimester of Pregnancy J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 833 - 839. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kyo, M. Nakamura, T. Kiyono, Y. Maida, T. Kanaya, M. Tanaka, N. Yatabe, and M. Inoue Successful Immortalization of Endometrial Glandular Cells with Normal Structural and Functional Characteristics Am. J. Pathol., December 1, 2003; 163(6): 2259 - 2269. [Abstract] [Full Text]
|
|
|
|
 |
|
 E. Mandelin, H. Lassus, M. Seppala, A. Leminen, J.-A. Gustafsson, G. Cheng, R. Butzow, and R. Koistinen Glycodelin in Ovarian Serous Carcinoma: Association with Differentiation and Survival Cancer Res., October 1, 2003; 63(19): 6258 - 6264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. I. Risinger, G. L. Maxwell, G. V. R. Chandramouli, A. Jazaeri, O. Aprelikova, T. Patterson, A. Berchuck, and J. C. Barrett Microarray Analysis Reveals Distinct Gene Expression Profiles among Different Histologic Types of Endometrial Cancer Cancer Res., January 1, 2003; 63(1): 6 - 11. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Seppala, R. N. Taylor, H. Koistinen, R. Koistinen, and E. Milgrom Glycodelin: A Major Lipocalin Protein of the Reproductive Axis with Diverse Actions in Cell Recognition and Differentiation Endocr. Rev., August 1, 2002; 23(4): 401 - 430. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Arnold, B. A. Lessey, M. Seppala, and D. G. Kaufman Effect of Normal Endometrial Stroma on Growth and Differentiation in Ishikawa Endometrial Adenocarcinoma Cells Cancer Res., January 1, 2002; 62(1): 79 - 88. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. B. C. Apparao, M. J. Murray, M. A. Fritz, W. R. Meyer, A. F. Chambers, P. R. Truong, and B. A. Lessey Osteopontin and Its Receptor {alpha}v{beta}3 Integrin Are Coexpressed in the Human Endometrium during the Menstrual Cycle But Regulated Differentially J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4991 - 5000. [Abstract] [Full Text] [PDF]
|
|