From the first discovery of ferritin as key component in organism survival via capturing and buffering the intracellular iron pool, many other different roles have been attributed to this molecule, including activities in angiogenesis and cancer development and maintenance. The iron-free form of the protein is composed of 24 subunits belonging to two subtypes termed H (heavy chain, FHC) and L (light chain, FLC). In pathological conditions as malignancies, the increased ferritin level is also associated with a shift in the composition of ferritin to more H-rich species. The aim of this work was to determine phenotypic properties of FHC-expressing and FHC shRNA-silenced Human Ovarian Carcinoma Cell Line (OVCAR3). We have found that FHC-silencing in OVCAR3 cells is accompanied by an increased cancer cell migration, by an increased colony formation and by an enhanced assumption of glucose from the culture medium. We have previously reported a list of proteins directly or indirectly controlled by FHC-silencing in human metastatic melanoma cells that includes galectin-1 (Gal-1) and galectin-3 (Gal-3), two lectins clearly involved in neoplastic transformation and metastasis. Gal-1 is overexpressed in shFHC cells with respect to un-silenced cells, whereas no variations were reported for Gal-3. While Gal-1 expression in tumor cells has been previously reported to be associated with enhanced tumor progression, we attempted to assess the involvement of Gal-1 as key mediator of FHC-silencing-dependent increase of cell migration. For this part, migratory capacities of FHC-expressing cells, shRNA control and shFHC cells were evaluated in the presence of anti-Gal-1 in a migration assay. Using this approach, we found a more significant decrease in the migration capacity of shFHC cells than the control groups. These results demonstrate that Gal-1 mediates FHC-silencing-dependent increase of cell migration. Overall, our data provide evidence demonstrating FHC role in OVCAR3 cells phenotype via alterations of Gal-1 expression, with critical implications in tumor biology.
FHC-silencing in OVCAR3 is accompanied by Gal-1 overexpression
Faniello C;Costanzo F;Barni T;Di Vito A
2013-01-01
Abstract
From the first discovery of ferritin as key component in organism survival via capturing and buffering the intracellular iron pool, many other different roles have been attributed to this molecule, including activities in angiogenesis and cancer development and maintenance. The iron-free form of the protein is composed of 24 subunits belonging to two subtypes termed H (heavy chain, FHC) and L (light chain, FLC). In pathological conditions as malignancies, the increased ferritin level is also associated with a shift in the composition of ferritin to more H-rich species. The aim of this work was to determine phenotypic properties of FHC-expressing and FHC shRNA-silenced Human Ovarian Carcinoma Cell Line (OVCAR3). We have found that FHC-silencing in OVCAR3 cells is accompanied by an increased cancer cell migration, by an increased colony formation and by an enhanced assumption of glucose from the culture medium. We have previously reported a list of proteins directly or indirectly controlled by FHC-silencing in human metastatic melanoma cells that includes galectin-1 (Gal-1) and galectin-3 (Gal-3), two lectins clearly involved in neoplastic transformation and metastasis. Gal-1 is overexpressed in shFHC cells with respect to un-silenced cells, whereas no variations were reported for Gal-3. While Gal-1 expression in tumor cells has been previously reported to be associated with enhanced tumor progression, we attempted to assess the involvement of Gal-1 as key mediator of FHC-silencing-dependent increase of cell migration. For this part, migratory capacities of FHC-expressing cells, shRNA control and shFHC cells were evaluated in the presence of anti-Gal-1 in a migration assay. Using this approach, we found a more significant decrease in the migration capacity of shFHC cells than the control groups. These results demonstrate that Gal-1 mediates FHC-silencing-dependent increase of cell migration. Overall, our data provide evidence demonstrating FHC role in OVCAR3 cells phenotype via alterations of Gal-1 expression, with critical implications in tumor biology.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
