Components of the hematopoietic compartments in tumor stroma and tumor-bearing mice.
Components of the hematopoietic compartments in tumor stroma and tumor-bearing mice.
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DOI：
10.1371/journal.pone.0018054
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发表时间：
2011-03-25
期刊：
影响因子：
3.7
通讯作者：
Zhang CC
中科院分区：
文献类型：
--
作者：
Huynh H;Zheng J;Umikawa M;Silvany R;Xie XJ;Wu CJ;Holzenberger M;Wang Q;Zhang CC
实体瘤由癌细胞和非癌间质组成。更好地了解肿瘤间质可能会导致新的治疗应用。然而，肿瘤间质的确切组成和功能在很大程度上仍然未知。在这里，我们使用一个刘易斯肺癌植入小鼠模型，研究了肿瘤间质和荷瘤小鼠的造血成分。不同谱系的分化造血细胞存在于肿瘤间质中，随着时间的推移，髓系细胞的百分比增加，淋巴系和红系细胞的百分比减少。利用骨髓重建分析，我们发现肿瘤间质也含有功能性造血干细胞。肿瘤间质中的造血细胞均来源于骨髓。在荷瘤小鼠的骨髓和外周血中，随着时间的推移，骨髓细胞群增加，淋巴细胞群和红细胞群减少，造血干细胞数量显著增加。为了研究造血细胞在肿瘤间质中的功能，我们将各种类型的造血细胞与癌细胞共植入。我们发现肿瘤间质中的全部造血细胞促进肿瘤的发展。此外，在用IGF I型受体缺陷型造血干细胞重建的小鼠中，原发性植入的刘易斯肺癌的生长及其转移显著降低，表明造血肿瘤基质中的IGF信号传导支持肿瘤生长。这些结果表明，造血细胞在肿瘤间质调节肿瘤的发展和肿瘤的进展显着改变宿主造血区室。
Solid tumors are composed of cancerous cells and non-cancerous stroma. A better understanding of the tumor stroma could lead to new therapeutic applications. However, the exact compositions and functions of the tumor stroma are still largely unknown. Here, using a Lewis lung carcinoma implantation mouse model, we examined the hematopoietic compartments in tumor stroma and tumor-bearing mice. Different lineages of differentiated hematopoietic cells existed in tumor stroma with the percentage of myeloid cells increasing and the percentage of lymphoid and erythroid cells decreasing over time. Using bone marrow reconstitution analysis, we showed that the tumor stroma also contained functional hematopoietic stem cells. All hematopoietic cells in the tumor stroma originated from bone marrow. In the bone marrow and peripheral blood of tumor-bearing mice, myeloid populations increased and lymphoid and erythroid populations decreased and numbers of hematopoietic stem cells markedly increased with time. To investigate the function of hematopoietic cells in tumor stroma, we co-implanted various types of hematopoietic cells with cancer cells. We found that total hematopoietic cells in the tumor stroma promoted tumor development. Furthermore, the growth of the primary implanted Lewis lung carcinomas and their metastasis were significantly decreased in mice reconstituted with IGF type I receptor-deficient hematopoietic stem cells, indicating that IGF signaling in the hematopoietic tumor stroma supports tumor outgrowth. These results reveal that hematopoietic cells in the tumor stroma regulate tumor development and that tumor progression significantly alters the host hematopoietic compartment.
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