Connexin Over-Expression Differentially Suppresses Glioma Growth and Contributes to the Bystander Effect Following HSV-Thymidine Kinase Gene Therapy |
| |
Authors: | Tomas Jimenez W Paul Fox Christian C G Naus Jacques Galipeau Daniel J Belliveau |
| |
Institution: |
a Department of Anatomy & Cell Biology, The University of Western Ontario, London, Ontario, Canada
b Department of Cellular & Physiological Sciences, The University of British Columbia, Life Sciences Centre, Vancouver, British Columbia, Canada
c Department of Medicine, Division of Hematology-Oncology, Lady Davis Institute for Medical Research, SMBD-Jewish General Hospital (McGill University), Montreal, Quebec, Canada |
| |
Abstract: | Neoplastic transformation is frequently associated with a loss of gap junctional intercellular communication and reduced expression of connexins. The introduction of connexin genes into tumor cells reverses the proliferative characteristics of such cells. However, there is very little comparative information on the effects of different connexins on cancer cell growth. We hypothesized that Cx26, Cx32, or Cx43 would display differential growth suppression of C6 glioma cells and uniquely modulate the bystander effect following transduction of C6 cells with HSVtk followed by suicide gene therapy. The bystander phenomenon is the death of a greater number of tumor cells than are expressing the HSVtk gene, presumably due to the passage of toxic molecules through gap junction channels. To test this hypothesis, we used retroviral vectors to infect C6 glioma cells producing connexin-expressing and HSVtk-expressing cell lines. All three connexin-expressing cell lines grew significantly slower than GFP-infected or native C6 cells. Cx32 and Cx26 were significantly more effective at mediating the bystander effect in cocultures of C6-connexin cells with C6-HSVtk cells. These studies indicate that connexins have unique properties that contribute to their tumor suppressive function. |
| |
Keywords: | connexin gap junction bystander effect thymidine kinase glioma gene therapy |
本文献已被 InformaWorld 等数据库收录! |
|