Origin of cancer-associated fibroblasts and tumor-associated macrophages in humans after sex-mismatched bone marrow transplantation.

Origin of cancer-associated fibroblasts and tumor-associated macrophages in humans after sex-mismatched bone marrow transplantation.
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DOI:
10.1038/s42003-018-0137-0
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发表时间:
2018
影响因子:
5.9
通讯作者:
Morii E
Morii E
中科院分区:
生物学2区
文献类型:
--
作者:
Kurashige M;Kohara M;Ohshima K;Tahara S;Hori Y;Nojima S;Wada N;Ikeda JI;Miyamura K;Ito M;Morii E

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肿瘤间质中的癌相关成纤维细胞(CAF)和肿瘤相关巨噬细胞(TAM)在疾病进展中起关键作用。最近使用小鼠模型的研究表明,CAF部分来源于骨髓,TAM主要来源于骨髓来源的炎性单核细胞。然而,这些细胞在人类中的起源仍不清楚。因此,我们研究了他们的人类起源,使用人类继发性肿瘤,性别不匹配的骨髓移植后,通过改良的免疫荧光原位杂交分析和三重免疫染色标本。我们观察到,骨髓移植后3-19年的乳腺、肝脏和口腔粘膜标本中的α-平滑肌肌动蛋白(αSMA)阳性CAFs大多数是骨髓源性细胞。相反,大多数瘤周α SMA阴性成纤维细胞样细胞实际上是骨髓来源的HLA-DR阳性髓样细胞,如巨噬细胞和树突状细胞。此外,几乎所有存在于非肿瘤区域中的CD 163阳性TAM和巨噬细胞都来源于骨髓。Masako Kurashige等人研究了人类癌症相关成纤维细胞和肿瘤相关巨噬细胞的起源。他们发现这些细胞来源于性别不匹配的骨髓移植后的骨髓。
Cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) in tumor stroma play a key role in disease progression. Recent studies using mice models suggest that CAFs are partly derived from bone marrow and TAMs primarily originate from bone marrow-derived inflammatory monocytes. However, the origin of these cells in humans remains unclear. Hence, we investigated their human origin, using specimens from human secondary tumors that developed after sex-mismatched bone marrow transplantation, by modified immunofluorescent in situ hybridization analysis and triple immunostaining. We observed that most of the α-smooth muscle actin (αSMA)-positive CAFs in the mammary gland, liver, and oral mucosa specimens obtained 3–19 years after bone marrow transplantation are recipient-derived cells. In contrast, the majority of the peritumoral αSMA-negative fibroblast-like cells are actually bone marrow-derived HLA-DR-positive myeloid cells, such as macrophages and dendritic cells. Furthermore, almost all CD163-positive TAMs and macrophages present in the non-tumor areas are derived from bone marrow. Masako Kurashige et al. investigate the origin of cancer-associated fibroblasts and tumor-associated macrophages in humans. They find that these are derived from bone marrow following sex-mismatched bone marrow transplants.
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