基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Does Diffusely Infiltrating Lobular Carcinoma of the Breast Arise from Epithelial-Mesenchymal Hybrid Cells?
Does Diffusely Infiltrating Lobular Carcinoma of the Breast Arise from Epithelial-Mesenchymal Hybrid Cells?
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经典弥漫浸润性小叶癌的影像学特征与起源于终末导管小叶单位和主要输乳管的乳腺癌不同。尽管“浸润性小叶癌”这一术语暗示其起源于乳腺小叶上皮内,但我们未能找到支持这一假设的证据。纤维结缔组织的异常增多以及独特的细胞结构,结合乳腺影像学上的异常特征,提示这种乳腺恶性肿瘤并非起源于衬覆乳腺导管和小叶的细胞。纤维腺体组织中唯一剩余的相关成分是间充质。从弥漫浸润性小叶癌病例中新鲜分离并培养的细胞含有同时具有上皮和间充质特性的上皮-间充质杂合细胞。肿瘤的影像学和组织病理学特征以及间充质干细胞阳性标志物 CD73、CD90 和 CD105 的表达均提示其向间充质转化方向发展。这些杂合细胞具有肿瘤起始潜能,并已被证明预后不良且对针对乳腺上皮来源恶性肿瘤的靶向治疗具有耐药性。我们的工作强调需要新的方法来诊断和治疗这一高度致命的乳腺癌亚型。
Classic diffusely infiltrating lobular carcinoma has imaging features divergent from the breast cancers originating from the terminal ductal lobular units and from the major lactiferous ducts. Although the term "invasive lobular carcinoma" implies a site of origin within the breast lobular epithelium, we were unable to find evidence supporting this assumption. Exceptional excess of fibrous connective tissue and the unique cell architecture combined with the aberrant features at breast imaging suggest that this breast malignancy has not originated from cells lining the breast ducts and lobules.
The only remaining relevant component of the fibroglandular tissue is the mesenchyme. The cells freshly isolated and cultured from diffusely infiltrating lobular carcinoma cases contained epithelial-mesenchymal hybrid cells with both epithelial and mesenchymal properties.
The radiologic and histopathologic features of the tumours and expression of the mesenchymal stem cell positive markers CD73, CD90, and CD105 all suggest development in the direction of mesenchymal transition. These hybrid cells have tumour-initiating potential and have been shown to have poor prognosis and resistance to therapy targeted for malignancies of breast epithelial origin.
Our work emphasizes the need for new approaches to the diagnosis and therapy of this highly fatal breast cancer subtype.
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