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A role for heterologous gap junctions between melanoma and endothelial cells in metastasis
Akihiko Ito, … , Hiroshi Yamasaki, Hiroshi Nojima
Akihiko Ito, … , Hiroshi Yamasaki, Hiroshi Nojima
Published May 1, 2000
Citation Information: J Clin Invest. 2000;105(9):1189-1197. https://doi.org/10.1172/JCI8257.
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Article

A role for heterologous gap junctions between melanoma and endothelial cells in metastasis

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Abstract

F10 and BL6 sublines of B16 mouse melanoma cells are metastatic after intravenous injection, but only BL6 cells are metastatic after subcutaneous injection. We found that connexin (Cx) 26 is upregulated in BL6 cells. To examine gap junction formation, we devised a coculture system, in which an opened vein segment was placed at the bottom of a culture dish and then dye-labeled melanoma cells were seeded onto it. Immunohistochemistry indicated that the vein segment preserved the integrity of the endothelial monolayer. In this system, BL6 cells could transfer dye into endothelial cells but F10 cells could not. Transfection with wild-type Cx26 rendered F10 cells competent for coupling with endothelial cells and as spontaneously metastatic as BL6 cells. Conversely, transfection with a dominant-negative form of Cx26 rendered BL6 cells deficient in coupling and less metastatic. In human melanoma lesions, the level of Cx26 expression was low in melanoma cells residing in the basal layer, but significantly upregulated in melanoma cells invading the dermis. The results suggested that Cx26 plays a role in intravasation and extravasation of tumor cells through heterologous gap junction formation with endothelial cells.

Authors

Akihiko Ito, Fumitaka Katoh, Tatsuki R. Kataoka, Morihito Okada, Noriaki Tsubota, Hideo Asada, Kunihiko Yoshikawa, Sakan Maeda, Yukihiko Kitamura, Hiroshi Yamasaki, Hiroshi Nojima

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Figure 1

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Expression of various connexins in F10 and BL6 cells and in the IVC segm...
Expression of various connexins in F10 and BL6 cells and in the IVC segment. (a) Northern blot analysis to detect the transcripts of Cx26, Cx32, Cx43, Cx37, and Cx40. As a positive control, mouse liver, heart and lung tissues, and SVEC4-10 cells were used. (b) Expression of Cx26 protein in F10 and BL6 cells. Cell lysates were extracted by alkaline treatment. Anti-Cx26 antibody detected monomeric Cx26 protein at approximately 24 kDa (indicated by an arrow in the right panel). Equal protein loading was confirmed by silver staining of the gel (left panel).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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