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Galectin-3 is a marker of favorable prognosis and a biologically relevant molecule in neuroblastic tumors.

Veschi V, Petroni M, Bartolazzi A, Altavista P, Dominici C, Capalbo C, Boldrini R, Castellano A, McDowell HP, Pizer B, Frati L, Screpanti I, Gulino A, Giannini G - Cell Death Dis (2014)

Bottom Line: Gal-3 expression is associated with the INPC histopathological categorization (P<0.001) and Shimada favorable phenotype (P=0.001), but not with other prognostically relevant features.Importantly, Gal-3 expression was associated with a better 5-year overall survival (P=0.003), and with improved cumulative survival in patient subsets at worse prognosis, such as older age at diagnosis, advanced stages or NB histopathological classification.Forced Gal-3 overexpression increased phenotypic differentiation and substrate adherence, while inhibiting proliferation.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Medicine, University La Sapienza, Rome, Italy.

ABSTRACT
Childhood neuroblastic tumors are characterized by heterogeneous clinical courses, ranging from benign ganglioneuroma (GN) to highly lethal neuroblastoma (NB). Although a refined prognostic evaluation and risk stratification of each tumor patient is becoming increasingly essential to personalize treatment options, currently only few biomolecular markers (essentially MYCN amplification, chromosome 11q status and DNA ploidy) are validated for this purpose in neuroblastic tumors. Here we report that Galectin-3 (Gal-3), a β-galactoside-binding lectin involved in multiple biological functions that has already acquired diagnostic relevance in specific clinical settings, is variably expressed in most differentiated and less aggressive neuroblastic tumors, such as GN and ganglioneuroblastoma, as well as in a subset of NB cases. Gal-3 expression is associated with the INPC histopathological categorization (P<0.001) and Shimada favorable phenotype (P=0.001), but not with other prognostically relevant features. Importantly, Gal-3 expression was associated with a better 5-year overall survival (P=0.003), and with improved cumulative survival in patient subsets at worse prognosis, such as older age at diagnosis, advanced stages or NB histopathological classification. In vitro, Gal-3 expression and nuclear accumulation accompanied retinoic acid-induced cell differentiation in NB cell lines. Forced Gal-3 overexpression increased phenotypic differentiation and substrate adherence, while inhibiting proliferation. Altogether, these findings suggest that Gal-3 is a biologically relevant player for neuroblastic tumors, whose determination by conventional immunohistochemistry might be used for outcome assessment and patient's risk stratification in the clinical setting.

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Related in: MedlinePlus

Increased Gal-3 expression and nuclear localization are induced by RA. (a) Phase contrast microphotographs documenting the morphological differentiation and the induction of neurites by RA on the N-type SK-N-BE(2)c and LAN-5 NB cell lines. Along with this effect, RA also induced the well-known downregulation of MYCN, and a dose dependent (b) Gal-3 increase at the mRNA and protein level as evidenced by Q-PCR (c, upper panel) and immunoblotting (c, lower panel), respectively, in both N-type NB cell lines. (d) Immunofluorescence analysis of Gal-3 expression on fixed SK-N-BE(2)c and LAN-5 cells showed that RA treatment promoted Gal-3 localization to the cell nucleus
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fig2: Increased Gal-3 expression and nuclear localization are induced by RA. (a) Phase contrast microphotographs documenting the morphological differentiation and the induction of neurites by RA on the N-type SK-N-BE(2)c and LAN-5 NB cell lines. Along with this effect, RA also induced the well-known downregulation of MYCN, and a dose dependent (b) Gal-3 increase at the mRNA and protein level as evidenced by Q-PCR (c, upper panel) and immunoblotting (c, lower panel), respectively, in both N-type NB cell lines. (d) Immunofluorescence analysis of Gal-3 expression on fixed SK-N-BE(2)c and LAN-5 cells showed that RA treatment promoted Gal-3 localization to the cell nucleus

Mentions: Gal-3 nuclear exclusion characterizes immature neuroblasts in several NB cases (Table 1, Figures 1c and d and Supplementary Table 1), consistent with data showing that MNA N-type (neuroblastic) NB cell lines express low levels of Gal-3 mostly localized in the cytoplasm34 (Figure 2d). Many MYCN-amplified cell lines undergo growth arrest, MYCN repression and neuronal differentiation upon treatment with the known neuronal differentiation factor all-trans retinoic acid (RA; Figures 2a–c).35, 36, 37 Along with these effects, RA also increased Gal-3 expression and promoted its nuclear accumulation in SK-N-BE2(c) and LAN-5 cell lines (Figures 2a–d).


Galectin-3 is a marker of favorable prognosis and a biologically relevant molecule in neuroblastic tumors.

Veschi V, Petroni M, Bartolazzi A, Altavista P, Dominici C, Capalbo C, Boldrini R, Castellano A, McDowell HP, Pizer B, Frati L, Screpanti I, Gulino A, Giannini G - Cell Death Dis (2014)

Increased Gal-3 expression and nuclear localization are induced by RA. (a) Phase contrast microphotographs documenting the morphological differentiation and the induction of neurites by RA on the N-type SK-N-BE(2)c and LAN-5 NB cell lines. Along with this effect, RA also induced the well-known downregulation of MYCN, and a dose dependent (b) Gal-3 increase at the mRNA and protein level as evidenced by Q-PCR (c, upper panel) and immunoblotting (c, lower panel), respectively, in both N-type NB cell lines. (d) Immunofluorescence analysis of Gal-3 expression on fixed SK-N-BE(2)c and LAN-5 cells showed that RA treatment promoted Gal-3 localization to the cell nucleus
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3973198&req=5

fig2: Increased Gal-3 expression and nuclear localization are induced by RA. (a) Phase contrast microphotographs documenting the morphological differentiation and the induction of neurites by RA on the N-type SK-N-BE(2)c and LAN-5 NB cell lines. Along with this effect, RA also induced the well-known downregulation of MYCN, and a dose dependent (b) Gal-3 increase at the mRNA and protein level as evidenced by Q-PCR (c, upper panel) and immunoblotting (c, lower panel), respectively, in both N-type NB cell lines. (d) Immunofluorescence analysis of Gal-3 expression on fixed SK-N-BE(2)c and LAN-5 cells showed that RA treatment promoted Gal-3 localization to the cell nucleus
Mentions: Gal-3 nuclear exclusion characterizes immature neuroblasts in several NB cases (Table 1, Figures 1c and d and Supplementary Table 1), consistent with data showing that MNA N-type (neuroblastic) NB cell lines express low levels of Gal-3 mostly localized in the cytoplasm34 (Figure 2d). Many MYCN-amplified cell lines undergo growth arrest, MYCN repression and neuronal differentiation upon treatment with the known neuronal differentiation factor all-trans retinoic acid (RA; Figures 2a–c).35, 36, 37 Along with these effects, RA also increased Gal-3 expression and promoted its nuclear accumulation in SK-N-BE2(c) and LAN-5 cell lines (Figures 2a–d).

Bottom Line: Gal-3 expression is associated with the INPC histopathological categorization (P<0.001) and Shimada favorable phenotype (P=0.001), but not with other prognostically relevant features.Importantly, Gal-3 expression was associated with a better 5-year overall survival (P=0.003), and with improved cumulative survival in patient subsets at worse prognosis, such as older age at diagnosis, advanced stages or NB histopathological classification.Forced Gal-3 overexpression increased phenotypic differentiation and substrate adherence, while inhibiting proliferation.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Medicine, University La Sapienza, Rome, Italy.

ABSTRACT
Childhood neuroblastic tumors are characterized by heterogeneous clinical courses, ranging from benign ganglioneuroma (GN) to highly lethal neuroblastoma (NB). Although a refined prognostic evaluation and risk stratification of each tumor patient is becoming increasingly essential to personalize treatment options, currently only few biomolecular markers (essentially MYCN amplification, chromosome 11q status and DNA ploidy) are validated for this purpose in neuroblastic tumors. Here we report that Galectin-3 (Gal-3), a β-galactoside-binding lectin involved in multiple biological functions that has already acquired diagnostic relevance in specific clinical settings, is variably expressed in most differentiated and less aggressive neuroblastic tumors, such as GN and ganglioneuroblastoma, as well as in a subset of NB cases. Gal-3 expression is associated with the INPC histopathological categorization (P<0.001) and Shimada favorable phenotype (P=0.001), but not with other prognostically relevant features. Importantly, Gal-3 expression was associated with a better 5-year overall survival (P=0.003), and with improved cumulative survival in patient subsets at worse prognosis, such as older age at diagnosis, advanced stages or NB histopathological classification. In vitro, Gal-3 expression and nuclear accumulation accompanied retinoic acid-induced cell differentiation in NB cell lines. Forced Gal-3 overexpression increased phenotypic differentiation and substrate adherence, while inhibiting proliferation. Altogether, these findings suggest that Gal-3 is a biologically relevant player for neuroblastic tumors, whose determination by conventional immunohistochemistry might be used for outcome assessment and patient's risk stratification in the clinical setting.

Show MeSH
Related in: MedlinePlus