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Latest Findings on the Effect of Gastrointestinal Microecology Remodeling of Tumor Microenvironment on Tumor Stemness
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摘要: 胃肠道微生态（gastrointestinal microecology, GM）系统由胃肠道正常菌群及生活的环境共同构成，对机体健康和诸多疾病的影响已经被广泛研究。GM系统对于肿瘤的影响主要体现在重塑肿瘤微环境（tumor microenvironment, TME）。TME是肿瘤生存的特殊微环境，可通过细胞间接触和分泌因子调节肿瘤细胞的特性，影响肿瘤发生发展。目前认为，肿瘤干细胞（cancer stem cell, CSC）模型是解释肿瘤起源和恶性进展的重要学说，CSC的形成和增殖往往代表着肿瘤侵袭转移和化疗耐药的增加，导致临床不良预后。因此，研究GM系统通过重塑TME而影响CSC特性获得，进而影响肿瘤侵袭转移和化疗耐药的作用和机制，对于临床上理解肿瘤恶性进展和改善肿瘤治疗效果有重要意义。然而由于胃肠道模型单菌含菌水平低、异质性大、远处转移不易溯源等因素，目前的研究还存在很大局限性。本文就GM重塑TME影响肿瘤干性获得及侵袭转移化疗耐药中的研究进展作出综述。Abstract: Gastrointestinal microecology (GM) system is composed of normal gut microbiota and its living environment. The impact of GM on human health and many diseases has been widely studied. The impact of GM system on tumors is mainly reflected in the remodeling of the tumor microenvironment (TME). TME, a special microenvironment that tumors live in, can regulate the characteristics of tumor cells and affect the occurrence and development of tumors through intercellular contact and the secretion of cytokines. At present, cancer stem cell (CSC) model is considered an important theory that explains the origin and malignant progression of tumors. The formation and proliferation of CSC usually represent increased tumor invasion, metastasis, and chemotherapy resistance, resulting in poor clinical prognosis in patients. Therefore, it is important to study the role and mechanism through which GM system affects the acquisition of CSC characteristics through remodeling TME, thereby affecting tumor invasion, metastasis, and chemotherapy resistance. Studies on this topic are of great significance for clinical understanding of tumor malignant progression and improving tumor treatment outcomes. However, due to the low content of single bacteria in the gastrointestinal model, high heterogeneity, and difficulty in tracing distant metastasis, there are still great limitations in the previous research. Herein, we reviewed the research progress in the effect of GM remodeling of TME on the acquisition of tumor stemness, tumor invasion and metastasis, and the resistance to chemotherapy.
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Key words:
- Gastrointestinal microecology /
- Tumor microenvironment /
- Cancer stem cell
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图 1 胃肠道微生态重塑肿瘤微环境激活干性相关通路，促进肿瘤干细胞形成
Figure 1. GM remodels TME to activate stemness-related pathways and promote the formation of CSC
LPS/LTA: lipopolysaccharide/lipoteichoic acid; SCFA: short chain fatty acid; Treg: regulatory T cell; ILC: innate lymphoid cell.
图 2 胃肠道微生态在胃癌、结直肠癌肿瘤干性获得中的作用及机制
Figure 2. The role and mechanism of GM in stemness acquisition of gastric cancer and colorectal cancer
Hp: Helicobacter pylori; CagA: cytotoxin-associated gene A; NF-κB: nuclear factor-kappa B; ICB: immune checkpoint blockade; SCFA: short chain fatty acid; ILC: innate lymphoid cell; IL: interleukin; ABHD5: abhydrolase domain containing 5.
图 3 胃肠道微生态在其他消化系统肿瘤干性获得中的作用及机制
Figure 3. The role and mechanism of GM in stemness acquisition of other digestive system tumors
MAMP: microbe-associated molecular patterns; LPS: lipopolysaccharide; LTA: lipoteichoic acid; TLR: Toll-like receptors; STAT3: signal transducer and activator of transcription 3; NF-κB: nuclear factor-kappa B; KRAS: kirsten rat sarcoma viral oncogene; Treg: regulatory T; IL: interleukin; TGF-β: transforming growth factor-beta.
图 4 胃肠道微生态在其他肿瘤干性获得中的作用及机制
Figure 4. The role and mechanism of GM in the stemness acquisition of other tumors
SCFA: short chain fatty acids; HDAC9: human histone deacetylase 9; Foxp3: forkhead box P3; TLR: Toll-like receptors; NF-κB: nuclear factor-kappa B; IL: interleukin; PAHs: polycyclic aromatic hydrocarbons.
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