Novel mechanism of tumorigenesis: increased transforming growth factor-beta 1 suppresses the expression of connexin 43 in BALB/cJ mice after implantation of poly-L-lactic acid.

Abstract

Poly-L-lactic acid (PLLA) is a widely used promising material for surgical implants such as tissue-engineered scaffolds. In this study, we aimed to determine the in vivo effect of PLLA plates on the cellular function of subcutaneous tissue in the two mouse strains, BALB/cJ and SJL/J, higher and lower tumorigenic strains, respectively. Gap-junctional intercellular communication (GJIC) and the expression of connexin 43 (Cx43) protein were significantly suppressed, whereas the secretion of transforming growth factor-beta 1 (TGF-beta 1) level was significantly increased in PLLA-implanted BALB/cJ mice compared with BALB/cJ controls. However, no significant difference in TGF-beta 1 secretion was observed between the SJL/J-implanted and SJL/J control mice. We found for the first time that a significant difference was observed between the two strains; thus, the PLLA increased the secretion of TGF-beta 1 and suppressed the mRNA expression of Cx43 at the earlier stage after implantation into the higher-tumorigenic strain, BALB/cJ mice. This novel mechanism might have a vital role in the inhibition of GJIC and promote the tumorigenesis in BALB/cJ mice.