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The type III transforming growth factor-β receptor inhibits proliferation, migration, and adhesion in human myeloma cells.

Publication ,  Journal Article
Lambert, KE; Huang, H; Mythreye, K; Blobe, GC
Published in: Mol Biol Cell
May 2011

Transforming growth factor-β (TGF-β) plays an important role in regulating hematopoiesis, inhibiting proliferation while stimulating differentiation when appropriate. We previously demonstrated that the type III TGF-β receptor (TβRIII, or betaglycan) serves as a novel suppressor of cancer progression in epithelial tumors; however, its role in hematologic malignancies is unknown. Here we demonstrate that TβRIII protein expression is decreased or lost in the majority of human multiple myeloma specimens. Functionally, restoring TβRIII expression in myeloma cells significantly inhibited cell growth, proliferation, and motility, largely independent of its ligand presentation role. In a reciprocal fashion, shRNA-mediated silencing of endogenous TβRIII expression enhanced cell growth, proliferation, and motility. Although apoptosis was not affected, TβRIII inhibited proliferation through induction of the cyclin-dependent kinase inhibitors p21 and p27. TβRIII further regulated myeloma cell adhesion, increasing homotypic myeloma cell adhesion while decreasing myeloma heterotropic adhesion to bone marrow stromal cells. Mechanistically, live cell imaging of myeloma and stroma cell cocultures revealed that TβRIII-mediated inhibition of heterotropic adhesion was associated with decreased duration of myeloma/bone marrow stromal cell interaction. These results suggest that loss of TβRIII expression during multiple myeloma progression contributes to disease progression through its functional effects on increased cell growth, proliferation, motility, and adhesion.

Duke Scholars

Published In

Mol Biol Cell

DOI

EISSN

1939-4586

Publication Date

May 2011

Volume

22

Issue

9

Start / End Page

1463 / 1472

Location

United States

Related Subject Headings

  • Stromal Cells
  • Signal Transduction
  • Receptors, Transforming Growth Factor beta
  • Proteoglycans
  • Multiple Myeloma
  • Immunoblotting
  • Humans
  • Hematopoiesis
  • Disease Progression
  • Developmental Biology
 

Citation

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MLA
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Lambert, K. E., Huang, H., Mythreye, K., & Blobe, G. C. (2011). The type III transforming growth factor-β receptor inhibits proliferation, migration, and adhesion in human myeloma cells. Mol Biol Cell, 22(9), 1463–1472. https://doi.org/10.1091/mbc.E10-11-0877
Lambert, Kathleen E., Huang Huang, Karthikeyan Mythreye, and Gerard C. Blobe. “The type III transforming growth factor-β receptor inhibits proliferation, migration, and adhesion in human myeloma cells.Mol Biol Cell 22, no. 9 (May 2011): 1463–72. https://doi.org/10.1091/mbc.E10-11-0877.
Lambert KE, Huang H, Mythreye K, Blobe GC. The type III transforming growth factor-β receptor inhibits proliferation, migration, and adhesion in human myeloma cells. Mol Biol Cell. 2011 May;22(9):1463–72.
Lambert, Kathleen E., et al. “The type III transforming growth factor-β receptor inhibits proliferation, migration, and adhesion in human myeloma cells.Mol Biol Cell, vol. 22, no. 9, May 2011, pp. 1463–72. Pubmed, doi:10.1091/mbc.E10-11-0877.
Lambert KE, Huang H, Mythreye K, Blobe GC. The type III transforming growth factor-β receptor inhibits proliferation, migration, and adhesion in human myeloma cells. Mol Biol Cell. 2011 May;22(9):1463–1472.

Published In

Mol Biol Cell

DOI

EISSN

1939-4586

Publication Date

May 2011

Volume

22

Issue

9

Start / End Page

1463 / 1472

Location

United States

Related Subject Headings

  • Stromal Cells
  • Signal Transduction
  • Receptors, Transforming Growth Factor beta
  • Proteoglycans
  • Multiple Myeloma
  • Immunoblotting
  • Humans
  • Hematopoiesis
  • Disease Progression
  • Developmental Biology