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大鼠脂肪来源的基质细胞(ADSCs)会促进胶质母细胞瘤的生长并降低动物存活率。

Rat Adipose-Derived Stromal Cells (ADSCs) Increases the Glioblastoma Growth and Decreases the Animal Survival.

作者信息

Iser Isabele Cristiana, Beckenkamp Liziane Raquel, Azambuja Juliana Hofstatter, Rahmeier Francine Luciano, Bracco Paula Andreghetto, Bertoni Ana Paula Santin, de Cássia Sant'Anna Alves Rita, Braganhol Elizandra, Xavier Léder Leal, da Cruz Fernandes Marilda, Lenz Guido, Wink Márcia Rosângela

机构信息

Departamento de Ciências Básicas da Saúde e Laboratório de Biologia Celular, Universidade Federal de Ciências da Saúde de Porto Alegre - UFCSPA, Rua Sarmento Leite, 245, Porto Alegre, RS, CEP 90050-170, Brazil.

Departamento de Ciências Básicas da Saúde e Laboratório de Pesquisa em Patologia, Universidade Federal de Ciências da Saúde de Porto Alegre - UFCSPA, Porto Alegre, RS, Brazil.

出版信息

Stem Cell Rev Rep. 2022 Apr;18(4):1495-1509. doi: 10.1007/s12015-021-10227-6. Epub 2021 Aug 17.

Abstract

Many studies have shown that mesenchymal stromal cells (MSCs) and their secreted factors may modulate the biology of tumor cells. However, how these interactions happen in vivo remains unclear. In the present study, we investigated the effects of rat adipose-derived stromal cells (ADSCs) and their conditioned medium (ADSC-CM) in glioma tumor growth and malignancy in vivo. Our results showed that when we co-injected C6 cells plus ADSCs into the rat brains, the tumors generated were larger and the animals exhibited shorter survival, when compared with tumors of the animals that received only C6 cells or C6 cells pre-treated with ADSC-CM. We further showed that the animals that received C6 plus ADSC did not present enhanced expression of CD73 (a gene highly expressed in ADSCs), indicating that the tumor volume observed in these animals was not a mere consequence of the higher density of cells administered in this group. Finally, we showed that the animals that received C6 + ADSC presented tumors with larger necrosis areas and greater infiltration of immune cells. These results indicate that the immunoregulatory properties of ADSCs and its contribution to tumor stroma can support tumor growth leading to larger zones of necrosis, recruitment of immune cells, thus facilitating tumor progression. Our data provide new insights into the way by which ADSCs and tumor cells interact and highlight the importance of understanding the fate and roles of MSCs in tumor sites in vivo, as well as their intricate crosstalk with cancer cells.

摘要

许多研究表明,间充质基质细胞(MSCs)及其分泌因子可能会调节肿瘤细胞的生物学特性。然而,这些相互作用在体内是如何发生的仍不清楚。在本研究中,我们调查了大鼠脂肪来源的基质细胞(ADSCs)及其条件培养基(ADSC-CM)对体内胶质瘤肿瘤生长和恶性程度的影响。我们的结果显示,当我们将C6细胞与ADSCs共同注射到大鼠脑内时,与仅接受C6细胞或经ADSC-CM预处理的C6细胞的动物所形成的肿瘤相比,所产生的肿瘤更大,且动物存活时间更短。我们进一步表明,接受C6加ADSCs的动物并未出现CD73(一种在ADSCs中高表达的基因)表达增强,这表明在这些动物中观察到的肿瘤体积并非仅仅是该组中所给予细胞密度更高的结果。最后,我们表明接受C6 + ADSCs的动物所形成的肿瘤坏死区域更大,免疫细胞浸润更明显。这些结果表明,ADSCs的免疫调节特性及其对肿瘤基质的贡献可支持肿瘤生长,导致更大的坏死区域、免疫细胞募集,从而促进肿瘤进展。我们的数据为ADSCs与肿瘤细胞相互作用的方式提供了新的见解,并突出了了解MSCs在体内肿瘤部位的命运和作用以及它们与癌细胞复杂串扰的重要性。

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