Connexin43 suppresses MFG-E8 while inducing contact growth inhibition of glioma cells

G. S. Goldberg, J. F. Bechberger, Y. Tajima, M. Merritt, Y. Omori, M. A. Gawinowicz, R. Narayanan, Y. Tan, Y. Sanai, H. Yamasaki, C. C G Naus, H. Tsuda, Bruce J Nicholson

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Gap junction expression has been reported to control the growth of a variety of transformed cells. We undertook parallel analysis of connexins Cx32 and Cx43 in glioma cells, which revealed potential mechanisms underlying this phenomenon and led to several novel findings. Cx43, but not Cx32, suppressed C6 glioma cell growth. Paradoxically, Cx32 transfection resulted in severalfold more dye transfer than Cx43. However, Cx43 transfectants shared endogenous metabolites more efficiently than Cx32 transfectants. Interestingly, a significant portion of Cx43 permeants were incorporated into macromolecules more readily than those that transferred via Cx32. Cx43 induced contact inhibition of cell growth but in contrast to other reports, did not affect log phase growth rates. Cell death, senescence, or suppression of growth factor signaling was not involved because no significant alterations were seen in cell viability, telomerase, or mitogen-activated protein kinase activity. However, suppression of cell growth by Cx43 entailed the secretion of growth-regulatory factors. Most notably, a major component of conditioned medium that was affected by Cx43 was found to be MFG-E8 (milk fat globule epidermal growth factor 8), which is involved in cell anchorage and integrin signaling. These results indicate that Cx43 regulates cell growth by the modulation of extracellular growth factors including MFG-E8. Furthermore, the ability of a Cx to regulate cell growth may rely on its ability to mediate the intercellular transfer of endogenous metabolites but not artificial dyes.

Original languageEnglish (US)
Pages (from-to)6018-6026
Number of pages9
JournalCancer Research
Volume60
Issue number21
StatePublished - Nov 1 2000
Externally publishedYes

Fingerprint

Contact Inhibition
Connexin 43
Epidermal Growth Factor
Glioma
Growth
Intercellular Signaling Peptides and Proteins
Coloring Agents
milk fat globule
Cell Aging
Telomerase
Gap Junctions
Conditioned Culture Medium
Mitogen-Activated Protein Kinases
Integrins
Transfection
Cell Survival
Cell Death

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Goldberg, G. S., Bechberger, J. F., Tajima, Y., Merritt, M., Omori, Y., Gawinowicz, M. A., ... Nicholson, B. J. (2000). Connexin43 suppresses MFG-E8 while inducing contact growth inhibition of glioma cells. Cancer Research, 60(21), 6018-6026.

Connexin43 suppresses MFG-E8 while inducing contact growth inhibition of glioma cells. / Goldberg, G. S.; Bechberger, J. F.; Tajima, Y.; Merritt, M.; Omori, Y.; Gawinowicz, M. A.; Narayanan, R.; Tan, Y.; Sanai, Y.; Yamasaki, H.; Naus, C. C G; Tsuda, H.; Nicholson, Bruce J.

In: Cancer Research, Vol. 60, No. 21, 01.11.2000, p. 6018-6026.

Research output: Contribution to journalArticle

Goldberg, GS, Bechberger, JF, Tajima, Y, Merritt, M, Omori, Y, Gawinowicz, MA, Narayanan, R, Tan, Y, Sanai, Y, Yamasaki, H, Naus, CCG, Tsuda, H & Nicholson, BJ 2000, 'Connexin43 suppresses MFG-E8 while inducing contact growth inhibition of glioma cells', Cancer Research, vol. 60, no. 21, pp. 6018-6026.
Goldberg GS, Bechberger JF, Tajima Y, Merritt M, Omori Y, Gawinowicz MA et al. Connexin43 suppresses MFG-E8 while inducing contact growth inhibition of glioma cells. Cancer Research. 2000 Nov 1;60(21):6018-6026.
Goldberg, G. S. ; Bechberger, J. F. ; Tajima, Y. ; Merritt, M. ; Omori, Y. ; Gawinowicz, M. A. ; Narayanan, R. ; Tan, Y. ; Sanai, Y. ; Yamasaki, H. ; Naus, C. C G ; Tsuda, H. ; Nicholson, Bruce J. / Connexin43 suppresses MFG-E8 while inducing contact growth inhibition of glioma cells. In: Cancer Research. 2000 ; Vol. 60, No. 21. pp. 6018-6026.
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