Plectin plays a role in the migration and volume regulation of astrocytes: a potential biomarker of glioblastoma

ZUGEC, Maja, Borut FURLANI, Maria J CASTANON, Bostjan RITUPER, Irmgard FISCHER, Giuseppe BROGGI, Rosario CALTABIANO, Giuseppe M V BARBAGALLO, Di Rosa MICHELINO, Daniele TIBULLO, Rosalba PARENTI, Nunzio VICARIO, Sasa SIMCIC, Victorio Martin POZO DEVOTO, Gorazd B STOKIN, Gerhard WICHE, Jernej JORGACEVSKI, Robert ZOREC a Maja POTOKAR. Plectin plays a role in the migration and volume regulation of astrocytes: a potential biomarker of glioblastoma. Journal of Biomedical Science. LONDON: BMC, 2024, roč. 31, č. 1, s. 1-22. ISSN 1021-7770. Dostupné z: https://dx.doi.org/10.1186/s12929-024-01002-z.

Základní údaje

• Originální název: Plectin plays a role in the migration and volume regulation of astrocytes: a potential biomarker of glioblastoma
• Autoři: ZUGEC, Maja, Borut FURLANI, Maria J CASTANON, Bostjan RITUPER, Irmgard FISCHER, Giuseppe BROGGI, Rosario CALTABIANO, Giuseppe M V BARBAGALLO, Di Rosa MICHELINO, Daniele TIBULLO, Rosalba PARENTI, Nunzio VICARIO, Sasa SIMCIC, Victorio Martin POZO DEVOTO (380 Itálie, domácí), Gorazd B STOKIN, Gerhard WICHE, Jernej JORGACEVSKI, Robert ZOREC a Maja POTOKAR.
• Vydání: Journal of Biomedical Science, LONDON, BMC, 2024, 1021-7770.

Další údaje

• Originální jazyk: angličtina
• Typ výsledku: Článek v odborném periodiku
• Obor: 10601 Cell biology
• Stát vydavatele: Velká Británie a Severní Irsko
• Utajení: není předmětem státního či obchodního tajemství
• WWW: URL
• Impakt faktor: Impact factor: 11.000 v roce 2022
• Organizační jednotka: Lékařská fakulta
• Doi: http://dx.doi.org/10.1186/s12929-024-01002-z
• UT WoS: 001147741700001
• Klíčová slova anglicky: Astrocyte; Glioblastoma; Plectin; Aquaporin 4; Intermediate filaments; Cytoskeleton; Edema; Cell volume; Cell migration
• Štítky: 14110517, rivok
• Příznaky: Mezinárodní význam, Recenzováno

Anotace

BackgroundThe expression of aquaporin 4 (AQP4) and intermediate filament (IF) proteins is altered in malignant glioblastoma (GBM), yet the expression of the major IF-based cytolinker, plectin (PLEC), and its contribution to GBM migration and invasiveness, are unknown. Here, we assessed the contribution of plectin in affecting the distribution of plasmalemmal AQP4 aggregates, migratory properties, and regulation of cell volume in astrocytes.MethodsIn human GBM, the expression of glial fibrillary acidic protein (GFAP), AQP4 and PLEC transcripts was analyzed using publicly available datasets, and the colocalization of PLEC with AQP4 and with GFAP was determined by immunohistochemistry. We performed experiments on wild-type and plectin-deficient primary and immortalized mouse astrocytes, human astrocytes and permanent cell lines (U-251 MG and T98G) derived from a human malignant GBM. The expression of plectin isoforms in mouse astrocytes was assessed by quantitative real-time PCR. Transfection, immunolabeling and confocal microscopy were used to assess plectin-induced alterations in the distribution of the cytoskeleton, the influence of plectin and its isoforms on the abundance and size of plasmalemmal AQP4 aggregates, and the presence of plectin at the plasma membrane. The release of plectin from cells was measured by ELISA. The migration and dynamics of cell volume regulation of immortalized astrocytes were assessed by the wound-healing assay and calcein labeling, respectively.ResultsA positive correlation was found between plectin and AQP4 at the level of gene expression and protein localization in tumorous brain samples. Deficiency of plectin led to a decrease in the abundance and size of plasmalemmal AQP4 aggregates and altered distribution and bundling of the cytoskeleton. Astrocytes predominantly expressed P1c, P1e, and P1g plectin isoforms. The predominant plectin isoform associated with plasmalemmal AQP4 aggregates was P1c, which also affected the mobility of astrocytes most prominently. In the absence of plectin, the collective migration of astrocytes was impaired and the dynamics of cytoplasmic volume changes in peripheral cell regions decreased. Plectin's abundance on the plasma membrane surface and its release from cells were increased in the GBM cell lines.ConclusionsPlectin affects cellular properties that contribute to the pathology of GBM. The observed increase in both cell surface and released plectin levels represents a potential biomarker and therapeutic target in the diagnostics and treatment of GBMs.

Návaznosti

• 964997, interní kód MU: Název: Alliance for Life Sciences: From Strategies to Actions in Central and Eastern Europe (Akronym: A4L_ACTIONS)

Investor: Evropská unie, Alliance for Life Sciences: From Strategies to Actions in Central and Eastern Europe, Health, demographic change and wellbeing (Societal Challenges)