Galectin‑3 blockade suppresses the growth of cetuximab‑resistant human oral squamous cell carcinoma

Yin, Peng; Cui, Shuanlong; Liao, Xueming; Yao, Xiaoguang

doi:10.3892/mmr.2021.12325

Cited by 6 publications

(4 citation statements)

References 49 publications

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“…This could impact recognition of these HNSCC cell surface glycoproteins by Galectins, given that α2-3 NeuAc carrying LacNAc epitopes can be recognised by Galectin 1 and 3, while the α2-6 NeuAc capping blocks this recognition [47]. In oral squamous cell carcinoma (OSCC), inhibition of Galectin-3 has been shown to overcome cetuximab-resistance in murine animal models [48]. Yin et al showed that in cetuximab-resistant OSCC tumours, increased expression of Galectin-3, p-ERK1/2 and p-Akt was observed.…”

Section: Discussionmentioning

confidence: 99%

Head and neck cancer N-glycome traits are cell line and HPV status–dependent

et al. 2022

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Glycosylation is the most common post-translational modification of proteins, and glycosylation changes at cell surfaces are frequently associated with malignant epithelia including head and neck squamous cell carcinoma (HNSCC). In HNSCC, 5-year survival remains poor, averaging around 50% globally: this is partly related to late diagnosis. Specific protein glycosylation signatures on malignant keratinocytes have promise as diagnostic and prognostic biomarkers and as therapeutic targets. Nevertheless, HNSCC-specific glycome is to date largely unknown. Herein, we tested six established HNSCC cell lines to capture the qualitative and semi-quantitative N-glycome using porous graphitized carbon liquid chromatography coupled to electrospray ionisation tandem mass spectrometry. Oligomannose-type N-glycans were the predominant features in all HNSCC cell lines analysed (57.5–70%). The levels of sialylated N-glycans showed considerable cell line-dependent differences ranging from 24 to 35%. Importantly, α2-6 linked sialylated N-glycans were dominant across most HNSCC cell lines except in SCC-9 cells where similar levels of α2-6 and α2-3 sialylated N-glycans were observed. Furthermore, we found that HPV-positive cell lines contained higher levels of phosphorylated oligomannose N-glycans, which hint towards an upregulation of lysosomal pathways. Almost all fucose-type N-glycans carried core-fucose residues with just minor levels (< 4%) of Lewis-type fucosylation identified. We also observed paucimannose-type N-glycans (2–5.5%), though in low levels. Finally, we identified oligomannose N-glycans carrying core-fucose residues and confirmed their structure by tandem mass spectrometry. This first systematic mapping of the N-glycome revealed diverse and specific glycosylation features in HNSCC, paving the way for further studies aimed at assessing their possible diagnostic relevance.

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Section: Discussionmentioning

confidence: 99%

Head and neck cancer N-glycome traits are cell line and HPV status–dependent

et al. 2022

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“…However, the application of cetuximab still has certain difficulties including mutations, toxicity/side effects, drug resistance and an optimal dosage to administer (35)(36)(37)(38). Furthermore, EGFR level detection needs to be performed prior to the administration of cetuximab.…”

Section: Discussionmentioning

confidence: 99%

HCRP‑1 alleviates the malignant phenotype and angiogenesis of oral squamous cell carcinoma cells via the downregulation of the EGFR/STAT3 signaling pathway

Yang

2022

Oncol Lett

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It has previously been reported that human hepatocellular carcinoma-related protein 1 (HCRP-1), which is a tumor suppressor gene, and epidermal growth factor receptor (EGFR) are abnormally expressed in certain solid tumors. Therefore, in the present study, the expression patterns of HCRP-1 in oral squamous cell carcinoma (OSCC) are discussed. Moreover, the present study investigated whether HCRP-1 regulated EGFR expression levels and its downstream effectors to further determine the regulation of tumor cell behavior. Therefore, the expression levels of HCRP-1 in normal oral epithelial and OSCC cells were determined, and the effects of HCRP-1 overexpression on OSCC cell proliferation, migration and invasion were assessed. Moreover, the culture medium from the different groups of OSCC cells was separately supplemented into the human umbilical vein endothelial cell (HUVEC) cultures, and the migration and angiogenesis of the HUVECs were assessed. To determine the roles of EGFR/STAT3 in the regulation of HCRP-1, EGF and colivelin, a STAT3 agonist, were used to treat CAL-27 cells and their effects on the cells were assessed using the aforementioned functional experiments. The results demonstrated that HCRP-1 expression levels were downregulated in OSCC cells and that HCRP-1 overexpression could suppress OSCC cell proliferation, migration and invasion. Moreover, the culture medium from OSCC cells overexpressing HCRP-1 facilitated the migration and angiogenesis of HUVECs. Furthermore, HCRP-1 was demonstrated to function in cells by regulating the EGFR/STAT3 signaling pathway. In summary, the present study indicated that HCRP-1 alleviated the malignant phenotype and angiogenesis of OSCC cells via the downregulation of the EGFR/STAT3 signaling pathway.

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“…These findings were realized by significant different GIII and GII (p-value = 0.002), and extremely significant difference between GIV and GII (p-value <0.001), this is in line with other studies. (77)(78)(79) This could explain as cetuximab blocked the activity of EGFR in cells that had a lot of EGFR auto-phosphorylation at the start of the cell, even though the cells did not have a lot of EGFR expression. EGFR signaling and how well EGFR suppression works are also based on other factors, like EGFR mutations and polymorphisms in the downstream pathways.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic efficacy of time-dependent cetuximab on experimentally induced hamster buccal pouch carcinoma

Shamia

Abd-Alhafez

Alqalshy

et al. 2022

ijhs

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Purpose: This study aimed to determine the cetuximab therapeutic potential in the time-dependent fashion in experimentally induced hamster buccal pouch (HBP) carcinoma. Material and methods: Forty Syrian male hamsters were classified into four equal groups (G) of ten each. GI: The animals remained untreated to act as negative controls. The right pouches of animals in GII, GIII, and GIV were painted three times a week for 14 weeks (w)s with 7,12-dimethylbenz (a) anthracene (DMBA). GII: No additional treatment was administered. While, the animals in GIII and GIV were treated differently. Those in GIII received cetuximab intraperitoneally (IP) three intervals a week for three (w)s, whereas those in GIV received cetuximab IP three intervals for six (w)s. After the end of the experiment, the gross observations were made, and blood samples (2ml) were withdrawn from the inner canthus of the eye for analysis of whole white blood cells (WBCs) and oxidative stress markers [glutathione (GSH) and malondialdehyde (MDA) levels]. All pouches were surgically bisected for preparation for Hematoxylin and Eosin (H&E) stain and immunohistochemistry (IHC) stain using epidermal growth factor receptor (EGFR). Other fresh tissue was used for DNA detection through a flow cytometry (FCM) test.

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Galectin‑3 blockade suppresses the growth of cetuximab‑resistant human oral squamous cell carcinoma

Cited by 6 publications

References 49 publications

Head and neck cancer N-glycome traits are cell line and HPV status–dependent

Head and neck cancer N-glycome traits are cell line and HPV status–dependent

HCRP‑1 alleviates the malignant phenotype and angiogenesis of oral squamous cell carcinoma cells via the downregulation of the EGFR/STAT3 signaling pathway

Therapeutic efficacy of time-dependent cetuximab on experimentally induced hamster buccal pouch carcinoma

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