Metastasis of nasopharyngeal carcinoma: What we know and do not know

Guo, Lingling; Wang, Haiyun; Zheng, Lixin; Wang, Ming‐Dian; Cao, Yun; Yang, Li; Liu, Zhijie; Peng, Li‐Xia; Huang, Bi‐Jun; Shao, Jian Yong; Qian, Chao‐Nan

doi:10.1051/vcm/2021003

Cited by 8 publications

(9 citation statements)

References 131 publications

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“…This suggests that sensitizing nasopharyngeal carcinoma cells to ferroptosis using inducers such as erastin, RSL3 or SOD2 inhibitors could be a viable strategy for inhibiting metastasis facilitated by IR. NPC has the highest metastatic potential among all head and neck cancers, [43,44] therefore; this antimetastasis strategy is worth exploring.…”

Section: Discussionmentioning

confidence: 99%

Depletion of SOD2 enhances nasopharyngeal carcinoma cell radiosensitivity via ferroptosis induction modulated by DHODH inhibition

Amos

Jiang

et al. 2023

BMC Cancer

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Background Recurrence due to the development of radioresistance remains a major challenge in the clinical management of nasopharyngeal carcinoma. The objective of this study was to increase the sensitivity of nasopharyngeal carcinoma cells to ionizing radiation by enhancing oxidative stress and ferroptosis caused by disrupting the mitochondrial anti-oxidant enzyme system. Methods Oxidative stress cell model was constructed by SOD2 knockdown using shRNA. The expression and activity of DHODH was suppressed by siRNA and brequinar in SOD2 depleted cells. Protein levels were determined by western blotting and ferroptosis was assessed by C11 BODIPY and malondialdehyde assay. Cell viability was evaluated using CCK-8 assay while radiotoxicity was assessed by colony formation assay. Cellular ATP level was determined by ATP assay kits, ROS was determined by DCFD and DHE, while mitochondrial oxygen consumption was determined by seahorse assay. Data were analyzed by two-tailed independent t-test. Results Radiation upregulated SOD2 expression and SOD2 depletion increased cellular O2.−, malondialdehyde, and the fluorescence intensity of oxidized C11 BODIPY. It also resulted in mitochondrial damage. Its depletion decreased colony formation both under ionizing and non-ionizing radiation conditions. The ferroptosis inhibitor, deferoxamine, rescued cell viability and colony formation in SOD2 depleted cells. Cellular level of malondialdehyde, fluorescence intensity of oxidized C11 BODIPY, O2.− level, ATP, and mitochondrial oxygen consumption decreased following DHODH inhibition in SOD2 depleted cells. Cell viability and colony formation was rescued by DHODH inhibition in SOD2 depleted cells. Conclusion Inducing oxidative stress by SOD2 inhibition sensitized nasopharyngeal carcinoma cells to ionizing radiation via ferroptosis induction. This was found to be dependent on DHODH activity. This suggests that DHODH inhibitors should be used with caution during radiotherapy in nasopharyngeal carcinoma patients.

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Section: Discussionmentioning

confidence: 99%

Depletion of SOD2 enhances nasopharyngeal carcinoma cell radiosensitivity via ferroptosis induction modulated by DHODH inhibition

Amos

Jiang

et al. 2023

BMC Cancer

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“…The spontaneous footpad to popliteal lymph node (LN) metastasis experiments were conducted as previously reported (Guo et al, 2021; Qian et al, 2006). Briefly, 1 × 10 5 cells in 20 μL DMEM were subcutaneously injected into the footpad of the left hind limb of each mouse to generate a primary tumor.…”

Section: Methodsmentioning

confidence: 99%

Ulinastatin inhibits the metastasis of nasopharyngeal carcinoma by involving uPA/uPAR signaling

Qiang

Liu

et al. 2023

Drug Development Research

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Distant metastasis is the primary reason for treatment failure in patients with nasopharyngeal carcinoma (NPC). In this study, we investigated the effect of ulinastatin (UTI) on NPC metastasis and its underlying mechanism. Highly‐metastatic NPC cell lines S18 and 58F were treated with UTI and the effect on cell proliferation, migration, and invasion were determined by MTS and Transwell assays. S18 cells with luciferase‐expressing (S18–1C3) were injected into the left hind footpad of nude mice to establish a model of spontaneous metastasis from the footpad to popliteal lymph node (LN). The luciferase messenger RNA (mRNA) was measured by quantitative polymerase chain reaction (qPCR), and the metastasis inhibition rate was calculated. Key molecular members of the UTI‐related uPA, uPAR, and JAT/STAT3 signaling pathways were detected by qPCR and immunoblotting. UTI suppressed the migration and infiltration of S18 and 5‐8F cells and suppressed the metastasis of S18 cells in vivo without affecting cell proliferation. uPAR expression decreased from 24 to 48 h after UTI treatment. The antimetastatic effect of UTI is partly due to the suppression of uPA and uPAR. UTI partially suppresses NPC metastasis by downregulating the expression of uPA and uPAR.

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“…In regions with high endemicity, the majority of NPC cases are detected at later stages, with roughly 10% of patients presenting with metastases at the time of identification. 3 NPC often metastasizes to the bone, lungs, liver, distant lymph nodes, and occasionally, the brain. Nonetheless, the occurrence of brain metastasis in NPC from endemic areas is low, and its underlying mechanism is unclear.…”

Section: Introductionmentioning

confidence: 99%

“…This review aims to provide a comprehensive understanding of NPC metastasis from multiple perspectives and identify potential avenues for future research on NPC. [2][3][4]…”

Section: Introductionmentioning

confidence: 99%

Nasopharyngeal Carcinoma: Metastases and Clinical Considerations

Dewi,

Ineka

2023

Advances in Health Sciences Research

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Nasopharyngeal carcinoma (NPC) is a challenging cancer due to its tendency for local recurrence and distant metastasis, with bone metastasis being the most common site of metastases. This review explores the etiological role of Epstein-Barr virus (EBV) infection in NPC tumorigenesis and discusses the clinical implications of NPC metastasis, including the most common patterns and the "seed and soil" theory. Risk factors associated with NPC are also addressed, including the consumption of salted fish, instant noodles, tobacco smoking, and exposure to carcinogenic substances such as wood dust, insecticides, and grilled food. Men and older individuals are at higher risk of developing distant metastases. Understanding the distant metastasis patterns in NPC is crucial for prognosis and treatment. Bone is the most common site of metastasis, and histological type and N3 stage are predictors of poor prognosis. Dual-site metastasis is more common than single-site metastasis, with identified trends in combined organ metastases. Further research is needed to better understand NPC metastasis and improve treatment outcomes.

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Metastasis of nasopharyngeal carcinoma: What we know and do not know

Cited by 8 publications

References 131 publications

Depletion of SOD2 enhances nasopharyngeal carcinoma cell radiosensitivity via ferroptosis induction modulated by DHODH inhibition

Depletion of SOD2 enhances nasopharyngeal carcinoma cell radiosensitivity via ferroptosis induction modulated by DHODH inhibition

Ulinastatin inhibits the metastasis of nasopharyngeal carcinoma by involving uPA/uPAR signaling

Nasopharyngeal Carcinoma: Metastases and Clinical Considerations

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