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Home / Equine Research Bank / J Biol Chem / Microvesicle-mediated Wnt/β-Catenin Signaling Promotes...
The Journal of biological chemistry2016; 291(47); 24390-24405; doi: 10.1074/jbc.M116.726117

Microvesicle-mediated Wnt/β-Catenin Signaling Promotes Interspecies Mammary Stem/Progenitor Cell Growth.

Abstract: Signaling mechanisms that regulate mammary stem/progenitor cell (MaSC) self-renewal are essential for developmental changes that occur in the mammary gland during pregnancy, lactation, and involution. We observed that equine MaSCs (eMaSCs) maintain their growth potential in culture for an indefinite period, whereas canine MaSCs (cMaSCs) lose their growth potential in long term cultures. We then used this system to investigate the role of microvesicles (MVs) in promoting self-renewal properties. We found that Wnt3a and Wnt1 were expressed at higher levels in MVs isolated from eMaSCs compared with those from cMaSCs. Furthermore, eMaSC-MVs were able to induce Wnt/β-catenin signaling in different target cells, including cMaSCs. Interestingly, the induction of Wnt/β-catenin signaling in cMaSCs was prolonged when using eMaSC-MVs compared with recombinant Wnt proteins, indicating that MVs are not only important for transport of Wnt proteins, but they also enhance their signaling activity. Finally, we demonstrate that the eMaSC-MVs-mediated activation of the Wnt/β-catenin signaling pathway in cMaSCs significantly improves the ability of cMaSCs to grow as mammospheres and, importantly, that this effect is abolished when eMaSC-MVs are treated with Wnt ligand inhibitors. This suggests that this novel form of intercellular communication plays an important role in self-renewal.
© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
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Publication Date: 2016-10-12 PubMed ID: 27733685PubMed Central: PMC5114396DOI: 10.1074/jbc.M116.726117Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research study discusses the role of microvesicles in enhancing the growth of interspecies mammary stem/progenitor cells by facilitating the Wnt/β-catenin signaling pathway. The findings suggest that microvesicles could potentially enhance the growth capabilities of mammary stem cells in cellular culture.

Overview of the Research Study

  • The primary objective of this research was to explore the signaling mechanisms that regulate mammary stem/progenitor cell (MaSC) self-renewal, which are critical for the developmental changes in the mammary gland during pregnancy, lactation, and involution.
  • The researchers noticed that equine MaSCs (eMaSCs) maintained their growth potential indefinitely when cultured, whereas canine MaSCs (cMaSCs) lost their growth potential during long term culture.
  • The variance in growth potential sparked interest in the role of microvesicles (MVs) in promoting cell growth.

Role of Microvesicles in Cell Growth

  • The research found that the Wnt3a and Wnt1, components of the Wnt/β-catenin signaling pathway known to regulate cell growth, were expressed in higher levels in MVs from eMaSCs as compared to those from cMaSCs.
  • Interestingly, the eMaSCs-derived MVs were able to induce Wnt/β-catenin signaling in different target cells, including cMaSCs.
  • Further, it was observed that the influence of this signaling on cMaSCs was more prolonged when eMaSC-MVs were used compared to when recombinant Wnt proteins were employed. This indicates that MVs not only transport Wnt proteins, but also enhance their signaling activity.

Significance of Wnt/β-Catenin Signaling in Cell Growth

  • The growth ability of cMaSCs improved significantly when eMaSC-MVs mediated the activation of the Wnt/β-catenin signaling pathway.
  • This growth enhancement was however not observed when the eMaSC-MVs were treated with Wnt ligand inhibitors, indicating that the activation of the pathway plays a key role in cell growth.
  • The findings suggest that this form of intercellular communication, facilitated by MVs, may play a significant role in cellular self-renewal.

Cite This Article

APA
Bussche L, Rauner G, Antonyak M, Syracuse B, McDowell M, Brown AMC, Cerione RA, Van de Walle GR. (2016). Microvesicle-mediated Wnt/β-Catenin Signaling Promotes Interspecies Mammary Stem/Progenitor Cell Growth. J Biol Chem, 291(47), 24390-24405. https://doi.org/10.1074/jbc.M116.726117

Publication

The Journal of biological chemistry
ISSN: 1083-351X
NlmUniqueID: 2985121R
Country: United States
Language: English
Volume: 291
Issue: 47
Pages: 24390-24405
PII: S0021-9258(20)34617-2

Researcher Affiliations

Bussche, Leen
  • From the Baker Institute for Animal Health and.
Rauner, Gat
  • From the Baker Institute for Animal Health and.
Antonyak, Marc
  • Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853 and.
Syracuse, Bethany
  • From the Baker Institute for Animal Health and.
McDowell, Melissa
  • From the Baker Institute for Animal Health and.
Brown, Anthony M C
  • the Department of Cell & Developmental Biology, Weill Cornell Medical College, New York, New York 10065.
Cerione, Richard A
  • Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853 and.
Van de Walle, Gerlinde R
  • From the Baker Institute for Animal Health and. Electronic address: grv23@cornell.edu.

MeSH Terms

  • Animals
  • Cell-Derived Microparticles / metabolism
  • Dogs
  • Female
  • Horses
  • Humans
  • Mammary Glands, Human / cytology
  • Mammary Glands, Human / metabolism
  • Pregnancy
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Wnt Signaling Pathway / physiology
  • Wnt1 Protein / metabolism
  • Wnt3A Protein / metabolism

Grant Funding

  • R21 CA186981 / NCI NIH HHS

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