Systemic Inflammation in Cachexia - Is Tumor Cytokine Expression Profile the Culprit?
Systemic Inflammation in Cachexia - Is Tumor Cytokine Expression Profile the Culprit?
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DOI：
10.3389/fimmu.2015.00629
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发表时间：
2015
影响因子：
7.3
通讯作者：
Seelaender M
中科院分区：
文献类型：
--
作者：
de Matos-Neto EM;Lima JD;de Pereira WO;Figuerêdo RG;Riccardi DM;Radloff K;das Neves RX;Camargo RG;Maximiano LF;Tokeshi F;Otoch JP;Goldszmid R;Câmara NO;Trinchieri G;de Alcântara PS;Seelaender M
恶病质影响约80%的胃肠道癌症患者。这种多因素综合征导致非自愿和持续的体重减轻，伴有全身炎症和免疫细胞浸润各种组织。了解肿瘤、免疫细胞和外周组织之间的相互作用有助于减轻全身炎症。因此，我们研究了具有相同诊断的体重稳定和恶病质癌症患者的皮下脂肪组织和肿瘤中的炎症，以建立肿瘤微环境和脂肪组织分泌模式与全身炎症之间的相关性。通过流式细胞术鉴定皮下和肿瘤血管间质部分的浸润单核细胞表型。分别用qRT-PCR和Multiplex Magpix®系统测量炎症因子和趋化因子的基因和蛋白表达。皮下血管间质分数没有表现出差异方面的巨噬细胞亚型，而在肿瘤中，M2巨噬细胞的百分比降低恶病质患者相比，体重稳定的同行。CCL 3、CCL 4和IL-1β在恶病质组脂肪组织和肿瘤组织中的表达较高。在两种组织中，趋化因子与IL-1β呈正相关。肿瘤组织和脂肪组织中趋化因子和细胞因子的含量呈正相关。结果强烈表明，与具有相同肿瘤诊断的体重稳定的患者相比，恶病质患者中肿瘤和外周组织之间的串扰更明显。
Cachexia affects about 80% of gastrointestinal cancer patients. This multifactorial syndrome resulting in involuntary and continuous weight loss is accompanied by systemic inflammation and immune cell infiltration in various tissues. Understanding the interactions among tumor, immune cells, and peripheral tissues could help attenuating systemic inflammation. Therefore, we investigated inflammation in the subcutaneous adipose tissue and in the tumor, in weight stable and cachectic cancer patients with same diagnosis, in order to establish correlations between tumor microenvironment and secretory pattern with adipose tissue and systemic inflammation. Infiltrating monocyte phenotypes of subcutaneous and tumor vascular-stromal fraction were identified by flow cytometry. Gene and protein expression of inflammatory and chemotactic factors was measured with qRT-PCR and Multiplex Magpix® system, respectively. Subcutaneous vascular-stromal fraction exhibited no differences in regard to macrophage subtypes, while in the tumor, the percentage of M2 macrophages was decreased in the cachectic patients, in comparison to weight-stable counterparts. CCL3, CCL4, and IL-1β expression was higher in the adipose tissue and tumor tissue in the cachectic group. In both tissues, chemotactic factors were positively correlated with IL-1β. Furthermore, positive correlations were found for the content of chemoattractants and cytokines in the tumor and adipose tissue. The results strongly suggest that the crosstalk between the tumor and peripheral tissues is more pronounced in cachectic patients, compared to weight-stable patients with the same tumor diagnosis.