Lack of canonical activities of connexins in highly aggressive human prostate cancer cells
Journal
Biological Research
ISSN
0717-6287
Date Issued
2024-12-19
Author(s)
Catalina Asencio
Loreto Véliz
Emilia Flores-Faúndez
Lorena Azócar
Carolina E. Echeverría
Verónica Torres-Estay
Catalina Ramírez-Santelices
Paula Sotomayor
Jorge Cancino
Bredford Kerr
Fernandez Olivares, Ainoa
Juan C. Sáez
Alejandro S. Godoy
Type
journal-article
Abstract
<jats:title>Abstract</jats:title><jats:p>Connexins (Cxs) have the ability to form channels that allow the exchange of ions/metabolites between adjacent cells (gap junction channels, GJC) or between the intra- and extra-cellular compartments (hemichannels, HC). Cxs were initially classified as tumor suppressors. However, more recently, it has been shown that Cxs exert anti- and pro-tumorigenic effects depending on the cell and tissue context. In prostate cancer (PCa), the expression and functionality of Cxs remain highly controversial. Here, we analyzed the expression pattern of Cx26, Cx32, Cx37, Cx40, Cx43 and Cx45 in PCa cell lines with increasing levels of tumor aggressiveness (LNCaP < LNCaP-C4-2 < Du-145 < PC-3). In addition, GJ and HC activities were evaluated in the PCa cell lines using dye coupling and dye uptake assays, respectively. Lastly, the cellular localization of Cx26, Cx32, and Cx43 was analyzed in LNCaP and PC-3 cell lines using immunofluorescence analyses. Our results showed a positive association between the mRNA levels of Cx26, Cx37 and Cx45 and the degree of aggressiveness of PCa cells, a negative association in the case of Cx32 and Cx43, and no clear pattern for Cx40. At the protein level, a negative relationship between the expression of Cx26, Cx32 and Cx43 and the degree of aggressiveness of PCa cell lines was observed. No significant differences were observed for the expression of Cx37, Cx40, and Cx45 in PCa cell lines. At the functional level, only LNCaP cells showed moderate GJ activity and LNCaP and LNCaP-C4-2 cells showed HC activity. Immunofluorescence analyses confirmed that the majority of Cx26, Cx32, and Cx43 expression was localized in the cytoplasm of both LNCaP and PC3 cell lines. This data indicated that GJ and HC activities were moderately detected only in the less aggressive PCa cells, which suggest that Cxs expression in highly aggressive PCa cells could be associated to channel-independent roles.</jats:p>
Subjects
connexins
;
gap junctions
;
hemichannels
;
prostate cancer
;
cell line, tumor
;
connexin 26
;
connexins
;
gap junctions
;
humans
;
male
;
prostatic neoplasms
;
connexin 26
;
gap junction protein
;
gap junction
;
genetics
;
human
;
male
;
metabolism
;
pathology
;
prostate tumor
;
tumor cell line