Upregulation of galectin-7 in murine lymphoma cells is associated with progression toward an aggressive phenotype

Abstract

We have previously shown that ICAM-1-deficient mice were resistant to lymphoma dissemination of intravenously injected 164T2 lymphoma cells. Highly aggressive variants of this cell line, however, could overcome this resistance. To discern the complex pattern of gene expression involved in the evolution of aggressiveness in lymphoma cells, we compared the transcriptome of 164T2 cells with that of their aggressive variants using cDNA arrays. We identified several genes that were differentially expressed in nonmetastatic lymphoma cells and their metastatic variants. Galectin-7, associated with the development of chemically induced mammary carcinoma, was one such gene whose expression was significantly upregulated. We showed that it was constitutively expressed in aggressive variants, at both mRNA and protein levels. Galectin-7 expression in aggressive lymphoma cells was induced upon in vivo selection in several organs, including the thymus, the spleen and kidneys. We also showed that treatment of nonaggressive lymphoma cells with 5-aza-2 0 -deoxycytidine was sufficient to induce galectin-7 gene expression. This report is the first to show that galectin-7 is expressed in aggressive lymphoma.

A Novel Function for Galectin-7: Promoting Tumorigenesis by Up-regulatingMMP-9Gene Expression

“…We found that the most prominent change among the genes tested was the strong upregulation of galectin-7 (9). Specifically, we reported that galectin-7 was constitutively expressed in aggressive T lymphoma cells at both mRNA and protein levels.…”

“…We have previously shown that aggressive T lymphoma cells, but not their nonaggressive parental cells, expressed galectin-7 at the protein level (9), suggesting that galectin-7 may have a role in tumorigenesis. To test this hypothesis, we thus transduced the nonaggressive 267 T lymphoma cells with murine galectin-7 cDNA.…”

La galectine-7 : un nouveau gène associé au pouvoir métastatique

“…Des calculs de vitesse de migration réa-lisés lors de la fermeture de blessures montrent que les cellules exprimant la toxine tétanique (TeNT) sauvage ont une vitesse de migration réduite de moitié par rapport aux cellules exprimant une forme mutée de la toxine tétanique. La cellubrévine joue donc un rôle important dans la migration cellulaire [3]. L'équipe de M.G.…”

“…Les cellules en migration, en bordure de blessure, exprimant la TeNT mutante, contrairement à celles exprimant la TeNT sauvage, internalisent un anticorps anti-β1-intégrine. Dans ces cellules, la Cb colocalise avec la β1-intégrine endocytée [3]. La Cb joue donc un rôle important dans la migration cellulaire en régulant l'adhérence des cellules au substrat médiée par la β1-intégrine.…”

“…Les événements post-homing se produisent donc lors des dernières étapes du processus métastatique, c'est-à-dire lorsque les cellules cancéreuses sortent de la circulation sanguine pour migrer à travers le parenchyme de l'organe cible, se frayant un chemin à travers la matrice extracellulaire afin de s'éta-blir pour donner naissance à la formation de tumeurs secondaires. L'analyse comparative des transcriptomes des cellules non agressives et des variants hautement métastatiques nous a permis d'identifier plusieurs gènes dont l'expression était modulée de façon significative lors de la transition vers un phénotype agressif [3]. Parmi ces gènes, nous avons observé une forte augmentation de l'expression du gène de la galectine-7 (Figure 1).…”