Although its precise function has not yet been established, galectin-1 seems to play a role in tumor progression. In this study, we investigated galectin-1 mRNA expression in human glioma specimens and glioma cell lines. Northern blot analysis showed higher galectin-1 mRNA levels in glioma tissues. The 0.7-kb galectin-1 mRNA transcript was detected, and the expression level correlated with the malignant state, from low-grade astrocytoma to glioblastoma. In several human glioma specimens, immunohistochemical examination with antiserum against a synthetic peptide corresponding to the predicted C-terminal sequence of the protein showed high levels of galectin-1 expression. To clarify the correlation between the expression of galectin-1 and the malignancy of gliomas, we examined whether expression of antisense galectin-1 would suppress tumor growth in rat 9L cells that express high levels of galectin-1. The cells were transfected with a plasmid DNA that produces antisense galectin-1 mRNA under the control of the metallothionein promoter, and stable clones expressing low levels of galectin-1 protein in comparison with control clones were isolated. Cells with low levels of galectin-1 displayed dramatic phenotypic changes in their morphology and growth properties compared with vector-transfected control 9L cells. Our data suggest that decreased expression of galectin-1 may arrest the growth of rat 9L cells.
We previously reported that schwannoma-derived growth factor (SDGF), a member of heparin-binding epidermal growth factor (EGF) family, participates in autocrine pathways and promotes rat glioma cell growth. To investigate the potential role of similar molecules in human gliomas, we examined 7 human glioma cell lines and 11 glioblastoma specimens for expression of the human homologue of SDGF, amphiregulin (AR), as well as heparin-binding EGF-like growth factor (HB-EGF). Northern blot analysis revealed that only one cell line and no tumor specimens expressed AR mRNA. In contrast, HB-EGF mRNA was expressed in all human glioma cell lines and its level of expression was two- to five-fold higher than that of control brain tissues in 8 of 11 glioblastoma cases. Immunohistochemistry demonstrated that membrane-anchored HB-EGF (proHB-EGF) and EGFR were co-expressed in 44% of 34 human malignant gliomas. Introduction of exogenous HB-EGF (10 ng/ml) increased human glioma cell proliferation, and anti-HB-EGF blocking antibodies reduced the growth of glioma cells by 30-40%, confirming the presence of an autocrine loop. When added to the medium, transforming growth factor-alpha, basic fibroblast growth factor, or HB-EGF rapidly induced HB-EGF mRNA expression. These results indicate that HB-EGF and proHB-EGF contribute to the growth of human malignant glioma cells, most likely through autocrine and juxtacrine mechanisms.
Ling Zhi-8 (LZ-8), a novel and recently discovered immunomodulatory protein having in vivo immuno-suppressive activity, was tested for in vivo effect against Type 1 (insulin-dependent) diabetes mellitus in the nonobese diabetic mouse, the disease having immunologically mediated aetiology in this animal. LZ-8 had mitogenic activity in vitro towards spleen cells of the non-obese diabetic mice as previously shown towards those of DBA/2 mice. Intraperitoneal administration of LZ-8 twice weekly into the mice (10.3-12.6 mg/kg body weight) from 4 weeks of age prevented insulitis and an almost normal number of insulin producing cells were observed. Extreme insulitis and reduction of the number of insulin producing cells were observed in the pancreata of the untreated non-obese diabetic mouse. No cumulative incidence of diabetes mellitus was observed in the LZ-8 treated group, while cumulative incidences of 70% and 60% were observed in an untreated group followed up to 42 weeks of age when the incidence of diabetes was defined as a plasma glucose level of greater than 11 mmol/l and as a urine glucose level of greater than 2+, respectively. T cell subset population analysis was performed to further investigate the action of LZ-8 on the non-obese diabetic mouse which revealed that LZ-8 treatment increased in L3T4'/Lyt-2+ ratio.
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