GPNMB-Positive Cells in Head and Neck Squamous Cell Carcinoma-Their Roles in Cancer Stemness, Therapy Resistance, and Metastasis.
GPNMB-Positive Cells in Head and Neck Squamous Cell Carcinoma-Their Roles in Cancer Stemness, Therapy Resistance, and Metastasis.
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DOI：
10.3389/pore.2022.1610450
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发表时间：
2022
影响因子：
2.8
通讯作者：
Omori, Yasufumi
中科院分区：
文献类型：
--
作者：
Kawasaki, Yohei;Suzuki, Hitomi;Suzuki, Shinsuke;Yamada, Takechiyo;Suzuki, Maya;Ito, Ayumi;Hatakeyama, Haruka;Miura, Masahito;Omori, Yasufumi
关键词：
目的：头颈部鳞状细胞癌（HNSCC）尽管采用了手术和放化疗的治疗方法，但预后仍然很差。免疫检查点抑制剂已被证明可以延长预期寿命，但疗效有限。糖蛋白非转移性黑色素瘤蛋白B（GPNMB）在乳腺癌治疗中受到了极大的关注，其中它与癌症干细胞（CSC）和上皮-间质转化（EMT）有关;然而，GPNMB在HNSCC中的功能完全未知。本研究旨在通过对临床标本进行免疫染色，阐明GPNMB阳性细胞的体外特征及其与预后的关系。 方法：我们在体外检测了GPNMB阳性细胞在四种HNSCC细胞系中的球体形成、侵袭和迁移能力。我们还用GPNMB对174例HNSCC患者的活检标本进行了免疫染色，以评估总生存率和无进展生存率。 结果如下：GPNMB阳性细胞表现出增强的球体形成、侵袭和迁移，表明它们可能具有CSC特征和诱导EMT的能力，如乳腺癌所报道的。临床标本显示，高表达组和低表达组的总生存率分别为39.4%和57.8%（p = 0.045），无进展生存率分别为27.6%和51.6%（p = 0.013），表明高GPNMB组预后不良。高GPNMB组对放化疗和生物放疗也更耐药。GPNMB在转移淋巴结中的表达高于原发肿瘤。 结论：GPNMB阳性细胞可能具有CSC特征并诱导EMT。对GPNMB在HNSCC中的功能进行详细的分析，并建立靶向GPNMB的治疗方法，将有助于改善HNSCC的预后。
Objective: Despite the use of surgical and chemoradiation therapies, head and neck squamous cell carcinoma (HNSCC) still has a poor prognosis. Immune checkpoint inhibitors have been shown to prolong life expectancy but have limited efficacy. Glycoprotein nonmetastatic melanoma protein B (GPNMB) has received significant attention in breast cancer treatment, in which it has been associated with cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT); however, the function of GPNMB in HNSCC is completely unknown. This study aimed to clarify the characteristics of GPNMB-positive cells in vitro and their association with the prognosis by immunostaining clinical specimens. Methods: We examined the sphere formation, invasion, and migration ability of GPNMB-positive cells in four HNSCC cell lines in vitro. We also immunostained biopsy specimens with GPNMB from 174 patients with HNSCC diagnosed, treated, and followed-up in our institution to evaluate overall survival and progression-free survival. Results: GPNMB-positive cells showed enhanced sphere formation, invasion, and migration, suggesting that they could have CSC characteristics and the ability to induce EMT, as reported for breast cancer. Clinical specimens showed that overall survival was 39.4% and 57.8% (p = 0.045) and that progression-free survival was 27.6% and 51.6% (p = 0.013) for the high-expression and the low-expression groups, respectively, indicating poor prognosis for the high GPNMB group. The high GPNMB group was also more resistant to chemoradiation and bioradiotherapy. GPNMB was more highly expressed in metastatic lymph nodes than in the primary tumor. Conclusion: GPNMB-positive cells might have CSC characteristics and induce EMT. Detailed functional analyses of GPNMB in HNSCC and the establishment of therapies targeting GPNMB will lead to improved prognoses.
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影响因子：
4.8
作者：
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通讯作者：
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