Mesenchymal Stem/Stromal Cells Exert Trophic Effect on Colorectal Cancer Metastasis to the Liver

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

Abstract

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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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
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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