| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Regular Article |
a Departments of Anatomy and Cell Biology and
b Pathology, The University of Western Ontario, London, Ontario, Canada N6A 5C1
Extravillous trophoblast (EVT) cells of the human placenta progressively lose their proliferative activity in situ as EVT cell columns migrate into and invade the decidua. It remains unclear whether this is due to a terminal differentiation of EVT cells along the invasive pathway with concomitant loss of proliferative ability, or a negative regulation by decidua-derived factors, or both mechanisms. Our earlier studies provided evidence for a negative regulation by a decidua-derived factor, transforming growth factor (TGF)-ß, which inhibited proliferation, migration, and invasiveness of first-trimester EVT cells in vitro. We further discovered that decidua also produces decorin, a proteoglycan that binds TGF-ß (and in some cases, inactivates TGF-ß), which is colocalized with TGF-ß in the decidual extracellular matrix. The present study used in vitro-propagated EVT cell lines to examine whether EVT cells retain their capacity for proliferation after the process of invasion; and whether decorin exerts any effect on EVT cell proliferation, migration, or invasiveness in a TGF-ß-dependent or TGF-ß-independent manner. We also examined whether trophoblastic cancer (choriocarcinoma) JAR and JEG-3 cells responded to decorin in a similar manner. Proliferation was measured using a colorimetric (MTT) cellularity assay and immunolabeling for the Ki-67 proliferation marker. Migration and invasiveness were measured in transwells by the ability of cells to cross 8-µm pores of polycarbonate membranes in the absence or presence of an additional matrigel barrier. These experiments revealed three points. First, EVT cells retained limited but significant proliferative ability in vitro after invading matrigel. Second, that decorin alone blocked EVT cell proliferation in a dose-dependent manner. This effect remained unaffected in an additional presence of TGF-ß, which exerted antiproliferative effects on its own. The antiproliferative effect of decorin was explained by an up-regulation of the p21 protein. Third, that decorin alone or TGF-ß alone exerted antimigratory and anti-invasive effects on EVT cells, but the addition of TGF-ß to decorin did not alter decorin action. And fourth, that choriocarcinoma cells were resistant to antiproliferative, antimigratory, and anti-invasive effects of decorin. These results suggest 1) that the invasive function of EVT cells is not associated with a terminal differentiation into a noncycling state; 2) that proliferation, migration, and invasiveness of EVT cells within the decidua are independently controlled by two decidual products, TGF-ß and decorin (decorin in the decidual extracellular matrix may serve as a storage mechanism for TGF-ß in an inactive state and may be activated by EVT cell proteolytic mechanisms, thus preventing overinvasion); and 3) that choriocarcinoma cells are refractory to negative regulation by both decidua-derived factors.
1 Supported by Canadian Institutes of Health Research grant MOP-14646 to P.K.L. and postdoctoral fellowships of the Lalor Foundation Inc. and National Science and Engineering Research Council of Canada to M.-J.G.
2 Correspondence. FAX: 519 661 3936; pklala{at}uwo.ca
3 These authors contributed equally to this work
This article has been cited by other articles:
|
|
 |
|
  D. Iacob, J. Cai, M. Tsonis, A. Babwah, C. Chakraborty, R. N. Bhattacharjee, and P. K. Lala Decorin-Mediated Inhibition of Proliferation and Migration of the Human Trophoblast via Different Tyrosine Kinase Receptors Endocrinology, December 1, 2008; 149(12): 6187 - 6197. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Nicola, P. K. Lala, and C. Chakraborty Prostaglandin E2-Mediated Migration of Human Trophoblast Requires RAC1 and CDC42 Biol Reprod, June 1, 2008; 78(6): 976 - 982. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Lockwood, C. Oner, Y. H. Uz, U. A. Kayisli, S. J. Huang, L. F. Buchwalder, W. Murk, E. F. Funai, and F. Schatz Matrix Metalloproteinase 9 (MMP9) Expression in Preeclamptic Decidua and MMP9 Induction by Tumor Necrosis Factor Alpha and Interleukin 1 Beta in Human First Trimester Decidual Cells Biol Reprod, June 1, 2008; 78(6): 1064 - 1072. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Gellersen, J. Briese, M. Oberndorfer, K. Redlin, A. Samalecos, D.-U. Richter, T. Loning, H.-M. Schulte, and A.-M. Bamberger Expression of the Metastasis Suppressor KAI1 in Decidual Cells at the Human Maternal-Fetal Interface: Regulation and Functional Implications Am. J. Pathol., January 1, 2007; 170(1): 126 - 139. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L Jones, C. Stoikos, J. K Findlay, and L. A Salamonsen TGF-{beta} superfamily expression and actions in the endometrium and placenta. Reproduction, August 1, 2006; 132(2): 217 - 232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Nie, Y. Li, K. Hale, H. Okada, U. Manuelpillai, E. M. Wallace, and L. A. Salamonsen Serine Peptidase HTRA3 Is Closely Associated with Human Placental Development and Is Elevated in Pregnancy Serum Biol Reprod, February 1, 2006; 74(2): 366 - 374. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Nicola, A. V. Timoshenko, S. J. Dixon, P. K. Lala, and C. Chakraborty EP1 Receptor-Mediated Migration of the First Trimester Human Extravillous Trophoblast: The Role of Intracellular Calcium and Calpain J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4736 - 4746. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Tartakover Matalon, A. Ornoy, A. Fishman, L. Drucker, and M. Lishner The effect of 6-mercaptopurine on early human placental explants Hum. Reprod., May 1, 2005; 20(5): 1390 - 1397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Xu, Y. Zhong, S. Munir, B. B. Yang, B. K. Tsang, and C. Peng Nodal Induces Apoptosis and Inhibits Proliferation in Human Epithelial Ovarian Cancer Cells via Activin Receptor-Like Kinase 7 J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5523 - 5534. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Goldoni, R. T. Owens, D. J. McQuillan, Z. Shriver, R. Sasisekharan, D. E. Birk, S. Campbell, and R. V. Iozzo Biologically Active Decorin Is a Monomer in Solution J. Biol. Chem., February 20, 2004; 279(8): 6606 - 6612. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
