间充质干细胞/间充质细胞在结直肠癌肝转移中的营养作用

Pratika Y Hern, Alex, er Pedroza-Gonzalez, L. V. D. Laan, M. Hoogduijn, M. Peppelenbosch, Q. Pan
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引用次数: 3

摘要

结直肠癌(CRC)是世界上第三大常见癌症。结直肠癌倾向于转移到肝脏,20%至70%的患者可能发生这种情况,是导致死亡的主要原因。间充质干细胞(Mesenchymal Stem/stromal cells, MSCs)已被证明能够迁移到结直肠癌部位,并在肿瘤进展中发挥重要作用。我们之前在肝脏中发现了一个常驻MSC人群。因此,本研究旨在探讨MSCs是否在CRC肝转移患者(CRC- lm)中浸润,以及其对肿瘤细胞生长的潜在影响。通过培养切除的患者CRC-LM组织,我们观察到成纤维细胞样细胞的出现。进一步的表型和功能表征证实了它们真正的MSCs特征。用一种成熟的MSCs标记物原位染色显示,CRC-LM患者中候选MSCs显著富集,尤其是肿瘤间质区域。此外,MSCs分泌的营养因子显著增加转移性结直肠癌细胞系的集落形成和生长。综上所述,我们在CRC-LM患者体内发现了MSCs的浸润和富集,而MSCs反过来又能滋养肿瘤细胞。
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Mesenchymal Stem/Stromal Cells Exert Trophic Effect on Colorectal Cancer Metastasis to the Liver
Colorectal Cancer (CRC) is the third most common cancer in the world. CRC tends to metastasize to the liver, which may occur in 20% to 70% of patients and represents the major cause of death. Mesenchymal Stem/stromal cells (MSCs) have shown to be able to migrate to CRC site and play an important role in tumor progression. We have previously identified a resident MSC population in the liver. Therefore, this study aims to investigate whether there is infiltration of MSCs into patient CRC Liver Metastasis (CRC-LM) and their potential effects on tumor cell growth. By culturing resected patient CRC-LM tissue, we observed the emerging of fibroblast-like cells. Further phenotype and functional characterization confirmed their bonafide MSCs features. In situ staining with a well-established MSCs marker showed a significant enrichment of candidate MSCs in patient CRC-LM, particularly the tumor-stromal area. Moreover, MSCs secreted trophic factors significantly increased colony formation and growth of a metastatic CRC cell line. In summary, we found infiltration and enrichment of MSCs in CRC-LM patient, which could in turn nourish tumor cells.
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