Galectin-7 as a potential predictive marker of chemo- and/or radio-therapy resistance in oral squamous cell carcinoma.
Bottom Line: Treatment of advanced oral squamous cell carcinoma (OSCC) requires the integration of multimodal approaches.The cumulative 5-year disease-specific survival rate was 75.2% in patients with resistant prediction using G7PS and 100% in patients with sensitive prediction.In vitro overexpression of galectin-7 significantly decreased cell viability in OSCC cell line.
Affiliation: Oral and Maxillofacial Surgery, Department of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.Show MeSH
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Mentions: To investigate the roles of galectin-7 in OSCC cells, the expression status of galectin-7 in six human OSCC cell lines was detected by Western blot analysis. A low endogenous expression of galectin-7 was detected in all OSCC cell lines except SKN3 (Fig. 7A). Next, we examined the effect of overexpressed galectin-7 in OSCC cells. HSC3 cells were infected with recombinant adenovirus encoding FLAG-tagged galectin-7 (Ad-FLAG-GAL7). The expression of galectin-7 was detected in a MOI-dependent manner with 1 μg/mL doxycycline by Western blot analysis (Fig. 7B), and we confirmed that FLAG-tagged galectin-7 was strongly expressed in HSC3 cells than endogenous expressions of galectin-7 in SKN3 or HSC2 cells (Fig. 7C). To examine the infection efficiency and intracellular distribution of Ad-FLAG-GAL7, we performed immunofluorescence labeling for overexpressed galectin-7. The infection efficiency of Ad-FLAG-GAL7 in HSC3 cells at MOI 50 was ∼80% (Fig. S1A). The intracellular distribution of Ad-FLAG-GAL7 was similar to the IHC staining pattern of galectin-7 (Fig. 8B). Moreover, by Western blot analysis, we confirmed that analysis of supernatants from HSC3 cells infected with Ad-FLAG-GAL7 or other OSCC cell lines have failed to provide evidence for a secreted form of galectin-7 (data not shown). To examine the effect of galectin-7 on cell viability, HSC3 cells infected with Ad-FLAG-GAL7 (MOI of 50) were cultured for 24 h with or without doxycycline. The overexpression of galectin-7 significantly decreased cell viability in normal culture conditions (Fig. 8A). Furthermore, similar results were observed when we treated the cells with 5 μg/mL cisplatin or 50 μg/mL 5-fluorouracil (Fig. 8A). These results indicate that galectin-7 may be involved in tumor cell proliferation/viability rather than chemosensitivity. We also investigated the role of galectin-7 using antisense galectin-7 oligonucleotides in OSCC cell lines. Unfortunately, the results showed no effects of galectin-7 knockdown on cell viability (Fig. S2). To determine whether the decreased cell viability was because of apoptosis, Ad-FLAG-GAL7-infected HSC3 cells were cultured with or without doxycycline. We observed weak activation and cleavage of caspase-3 induced by the overexpression of galectin-7 was observed (Fig. 8B) indicating that the decreased cell viability by overexpression of galectin-7 may be because of growth arrest rather than apoptosis.
Affiliation: Oral and Maxillofacial Surgery, Department of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.