甲状腺无节细胞癌:在小鼠异种移植模型中,波形蛋白在肿瘤的侵袭前沿分离。

IF 2.1 4区 生物学 Q4 CELL BIOLOGY Histochemistry and Cell Biology Pub Date : 2024-11-18 DOI:10.1007/s00418-024-02329-2
Alessandro Miraglia, Laura Giannotti, Francesco De Nuccio, Antonella Sonia Treglia, Michele Maffia, Dario Domenico Lofrumento, Bruno Di Jeso, Giuseppe Nicolardi
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引用次数: 0

摘要

甲状腺无节细胞癌(ATC)是致死率最高的人类癌症之一。迁移和侵袭能力的增强在恶性肿瘤中至关重要,而且往往是上皮-间质转化(EMT)的继发因素。然而,目前还不清楚ATC的侵袭行为是否与EMT的存在有关。在本研究中,我们使用鼠异种移植模型(4 周大雄性 BALB/c NU/NU 小鼠)和人类无性细胞系 FRO。我们采用了一种不依赖眼睛的自动方法来重建肿瘤的总面积/小面积。为了探究EMT,我们评估了肿瘤前部和中部间质/上皮标记物的免疫染色。移植细胞所形成的肿瘤块在组织学上与患者肿瘤非常相似。苏木精-伊红染色和细胞角蛋白 18(一种上皮标记物)免疫染色结果相似。然而,细胞角蛋白 18 的免疫染色与间质标志物波形蛋白的免疫染色却截然不同,因为波形蛋白的染色集中在肿瘤的前端,向肿瘤中心迅速下降。细胞角蛋白和波形蛋白染色经过颜色转换后的叠加图显示,前端的染色最为一致,而向中心的染色则迅速消失。结果显示,ATC前端有EMT迹象,这可能是其巨大侵袭性的基础。此外,在方法上,对肿瘤总面积/小面积的自动 "不依赖眼睛 "采集,促使我们选择了第二种高倍率的自动视野采集。未来的研究可能会从个性化诊断程序的角度扩展这些结果。
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Anaplastic thyroid carcinoma: vimentin segregates at the invasive front of tumors in a murine xenograft model.

Anaplastic thyroid carcinoma (ATC) ranks among the most lethal human cancers. Increased migratory and invasive capabilities are critical in malignancy and are often secondary to epithelial-mesenchymal transition (EMT). However, it is not clear whether the invasive behavior of ATC is associated with the presence of EMT. In this study, we used a murine xenograft model (4-week-old male BALB/c NU/NU mice) with the human anaplastic cell line, FRO. We adopted an automated, eye-independent method to reconstruct the total/subtotal area of the tumors. To probe EMT, we evaluated the immunostaining of mesenchymal/epithelial markers at the front and center of the tumors. The transplanted cells invariably gave rise to tumor masses that histologically closely replicated patient tumors. The staining with hematoxylin-eosin and immunostaining with cytokeratin 18, an epithelial marker, were similar. However, the immunostaining of cytokeratin 18 versus vimentin, a mesenchymal marker, were strikingly dissimilar, since vimentin showed a staining concentrated at the front, rapidly declining towards the center of the tumor. The overlay, after color conversion, of cytokeratin and vimentin staining showed maximal coincidence at the front, which was rapidly lost towards the center. The results show EMT signs at the front of the ATC, which are probably at the basis of its tremendous invasiveness. Moreover, methodologically, an automated "eye-independent" acquisition of the total/subtotal area of the tumors drove the selection of second, high-magnification, automated field acquisition. Future studies may extend these results along the perspective of a personalized diagnostic procedure.

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来源期刊
Histochemistry and Cell Biology
Histochemistry and Cell Biology 生物-细胞生物学
CiteScore
4.90
自引率
8.70%
发文量
112
审稿时长
1 months
期刊介绍: Histochemistry and Cell Biology is devoted to the field of molecular histology and cell biology, publishing original articles dealing with the localization and identification of molecular components, metabolic activities and cell biological aspects of cells and tissues. Coverage extends to the development, application, and/or evaluation of methods and probes that can be used in the entire area of histochemistry and cell biology.
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