Recurrent Spindle Cell Carcinoma Shows Features of Mesenchymal Stem Cells

Recurrent Spindle Cell Carcinoma Shows Features of Mesenchymal Stem Cells
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DOI:
10.1177/0022034518759278
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发表时间:
2018-03
影响因子:
7.6
通讯作者:
T. Ouchi;S. Morikawa;S. Shibata;M. Takahashi;M. Yoshikawa;T. Soma;H. Miyashita;W. Muraoka;K. Kameyama;H. Kawana;Y. Arima;H. Saya;H. Okano;T. Nakagawa;S. Asoda
T. Ouchi;S. Morikawa;S. Shibata;M. Takahashi;M. Yoshikawa;T. Soma;H. Miyashita;W. Muraoka;K. Kameyama;H. Kawana;Y. Arima;H. Saya;H. Okano;T. Nakagawa;S. Asoda
中科院分区:
医学1区
文献类型:
--
作者:
T. Ouchi;S. Morikawa;S. Shibata;M. Takahashi;M. Yoshikawa;T. Soma;H. Miyashita;W. Muraoka;K. Kameyama;H. Kawana;Y. Arima;H. Saya;H. Okano;T. Nakagawa;S. Asoda

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本文报告1例舌梭形细胞癌的临床表现。患者在手术干预后出现局部复发和远处转移。虽然给予标准化疗,肉芽肿性肿块继续发展。这种侵略性的生长导致了肿瘤的存活。应患者要求,进行了二次减瘤手术,以改善患者的生活质量。使用来自二次减积手术的组织样本,我们对肿瘤的细胞表面抗原、分化潜能、转移能力和抗癌试剂的抑制潜能进行了分析。体外分析显示,在贴壁培养条件下生长的细胞群表达间充质干细胞(MSC)标志物CD 73、CD 90和CD 105。从该SpCC建立的细胞系含有集落形成单位成纤维细胞(CFU-Fs),并表现出多能分化为几种间充质谱系,包括骨、软骨和脂肪。SpCC细胞也表现出强烈的动员。这些特征表明它们具有间充质细胞的分化潜能,尤其是MSCs,而不是上皮细胞。本研究中分析的手术标本对分子靶向试剂西妥昔单抗(一种表皮生长因子受体抑制剂)有抵抗力。这一临床发现表明,与对西妥昔单抗敏感的大多数其他癌细胞相比,耐化疗的SpCC细胞具有不同的特征。我们的细胞死亡试验显示,SpCC细胞死亡是由抗癌药物伊马替尼诱导的,伊马替尼已知可抑制ABL、血小板衍生生长因子受体α(PDGFRα)和KIT的蛋白酪氨酸激酶活性。在这里,我们报告了复发性SpCC与MSC的特点和伊马替尼治疗的潜力。
This study investigated a case of spindle cell carcinoma (SpCC) in tongue pathological lesions. The patient experienced a local recurrence and distant metastasis after surgical intervention. Although standard chemotherapy was administered, a granulomatous mass continued to develop. This aggressive growth led to survival of the tumor. Secondary debulking surgery was performed to improve the patient’s quality of life at the request of the patient. Using a tissue sample derived from the secondary debulking surgery, we performed an analysis of the tumor’s cell surface antigens, differentiation potential, metastatic ability, and inhibition potential by anticancer reagents. In vitro analysis revealed that the cell population grown under adherent culture conditions expressed the mesenchymal stem cell (MSC) markers CD73, CD90, and CD105. The cell line established from this SpCC contained colony-forming unit fibroblasts (CFU-Fs) and exhibited multipotent differentiation into several mesenchymal lineages, including bone, cartilage, and fat. The SpCC cells also displayed vigorous mobilization. These characteristics suggested that they had the differentiation potential of mesenchymal cells, especially MSCs, rather than that of epithelial cells. The surgical specimen analyzed in this study resisted the molecular target reagent cetuximab, which is an epidermal growth factor receptor inhibitor. This clinical insight revealed that chemotherapy-resistant SpCC cells have different characteristics compared to most other cancer cells, which are sensitive to cetuximab. Our cell death assay revealed that SpCC cell death was induced by the anticancer drug imatinib, which is known to inhibit protein tyrosine kinase activity of ABL, platelet-derived growth factor receptor α (PDGFRα), and KIT. Here, we report recurrent SpCC with characteristics of MSCs and potential for treatment with imatinib.