Three-dimensional growth of extravillous cytotrophoblasts promotes differentiation and invasion

H. L. LaMarca, C. M. Ott, K. Höner zu Bentrup, C. L. LeBlanc, D. L. Pierson, A. B. Nelson, A. B. Scandurro, G. St J Whitley, Cheryl Nickerson, C. A. Morris

Research output: Contribution to journalArticle

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Abstract

Human trophoblast research relies on a combination of in vitro models, including isolated primary cultures, explant cultures, and trophoblast cell lines. In the present study, we have utilized the rotating wall vessel (RWV) bioreactor to generate a three-dimensional (3-D) model of human placentation for the study of cytotrophoblast (CTB) invasion. The RWV supported the growth of the human CTB cell line SGHPL-4 and allowed for the formation of complex, multilayered 3-D aggregates that were morphologically, phenotypically, and functionally distinct from SGHPL-4 monolayers. The cells cultured three-dimensionally differentiated into an aggressively invasive cell population characterized by the upregulation of matrix metalloproteinase-2 (MMP-2), MMP-3, MMP-9 and urokinase-type plasminogen activator (uPA) secretion and activation. Microarray analysis of the 3-D and 2-D cultured cells revealed increased expression in the 3-D cells of various genes that are known mediators of invasion, including MT1-MMP, PECAM-1 and L-selectin, as well as genes not previously associated with CTB differentiation such as MMP-13 and MT5-MMP. These results were verified by quantitative real-time PCR. These findings suggest that when cultured in 3-D, SGHPL-4 cells closely mimic differentiating in utero CTBs, providing a novel approach for the in vitro study of the molecular mechanisms that regulate CTB differentiation and invasion.

Original languageEnglish (US)
Pages (from-to)709-720
Number of pages12
JournalPlacenta
Volume26
Issue number10
DOIs
StatePublished - Nov 2005
Externally publishedYes

Fingerprint

Trophoblasts
Matrix Metalloproteinases
Growth
Somatostatin-Secreting Cells
Cultured Cells
CD31 Antigens
Matrix Metalloproteinase 14
L-Selectin
Cell Line
Placentation
Matrix Metalloproteinase 2
Urokinase-Type Plasminogen Activator
Bioreactors
Microarray Analysis
Genes
Real-Time Polymerase Chain Reaction
Up-Regulation
Research
Population

Keywords

  • Cytotrophoblast
  • Differentiation
  • Invasion
  • Matrix metalloproteinase
  • Placentation
  • Pregnancy
  • Rotating wall vessel
  • Three-dimensional

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

LaMarca, H. L., Ott, C. M., Höner zu Bentrup, K., LeBlanc, C. L., Pierson, D. L., Nelson, A. B., ... Morris, C. A. (2005). Three-dimensional growth of extravillous cytotrophoblasts promotes differentiation and invasion. Placenta, 26(10), 709-720. https://doi.org/10.1016/j.placenta.2004.11.003

Three-dimensional growth of extravillous cytotrophoblasts promotes differentiation and invasion. / LaMarca, H. L.; Ott, C. M.; Höner zu Bentrup, K.; LeBlanc, C. L.; Pierson, D. L.; Nelson, A. B.; Scandurro, A. B.; Whitley, G. St J; Nickerson, Cheryl; Morris, C. A.

In: Placenta, Vol. 26, No. 10, 11.2005, p. 709-720.

Research output: Contribution to journalArticle

LaMarca, HL, Ott, CM, Höner zu Bentrup, K, LeBlanc, CL, Pierson, DL, Nelson, AB, Scandurro, AB, Whitley, GSJ, Nickerson, C & Morris, CA 2005, 'Three-dimensional growth of extravillous cytotrophoblasts promotes differentiation and invasion', Placenta, vol. 26, no. 10, pp. 709-720. https://doi.org/10.1016/j.placenta.2004.11.003
LaMarca HL, Ott CM, Höner zu Bentrup K, LeBlanc CL, Pierson DL, Nelson AB et al. Three-dimensional growth of extravillous cytotrophoblasts promotes differentiation and invasion. Placenta. 2005 Nov;26(10):709-720. https://doi.org/10.1016/j.placenta.2004.11.003
LaMarca, H. L. ; Ott, C. M. ; Höner zu Bentrup, K. ; LeBlanc, C. L. ; Pierson, D. L. ; Nelson, A. B. ; Scandurro, A. B. ; Whitley, G. St J ; Nickerson, Cheryl ; Morris, C. A. / Three-dimensional growth of extravillous cytotrophoblasts promotes differentiation and invasion. In: Placenta. 2005 ; Vol. 26, No. 10. pp. 709-720.
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AU - Pierson, D. L.

AU - Nelson, A. B.

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