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DU-145 prostate carcinoma cells that selectively transmigrate narrow obstacles express elevated levels of Cx43

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Abstract

The formation of aqueous intercellular channels mediating gap junctional intercellular coupling (GJIC) is a canonical function of connexins (Cx). In contrast, mechanisms of GJIC-independent involvement of connexins in cancer formation and metastasis remain a matter of debate. Because of the role of Cx43 in the determination of carcinoma cell invasive potential, we addressed the problem of the possible Cx43 involvement in early prostate cancer invasion. For this purpose, we analysed Cx43-positive DU-145 cell subsets established from the progenies of the cells most readily transmigrating microporous membranes. These progenies displayed motile activity similar to the control DU-145 cells but were characterized by elevated Cx43 expression levels and GJIC intensity. Thus, apparent links exist between Cx43 expression and transmigration potential of DU-145 cells. Moreover, Cx43 expression profiles in the analysed DU-145 subsets were not affected by intercellular contacts and chemical inhibition of GJIC during the transmigration. Our observations indicate that neither cell motility nor GJIC determines the transmigration efficiency of DU-145 cells. However, we postulate that selective transmigration of prostate cancer cells expressing elevated levels of Cx43 expression may be crucial for the “leading front” formation during cancer invasion.

Abbreviations

AGA:

18-α-glycyrrhetinic acid

ARCD:

average rate of cell displacement

ASCM:

average speed of cell movement

Cr :

coupling ratio

Cx43:

connexin43

DMEM:

Dulbecco modified Eagle’s medium

FBS:

fetal bovine serum

GJIC:

gap junctional intercellular coupling

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Correspondence to Jarosław Czyż.

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Key words

  • Cancer invasion
  • Cell heterogeneity
  • Cell motility
  • Cx43
  • Gap junctions
  • Metastasis
  • Prostate cancer
  • Transmigration