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细胞外基质重构在癌症的进展和转移中的后果以及新型免疫疗法:未来努力的巨大承诺。

Consequences of Extracellular Matrix Remodeling in Headway and Metastasis of Cancer along with Novel Immunotherapies: A Great Promise for Future Endeavor.

机构信息

Department of Applied Sciences, Indira Gandhi Technological and Medical Sciences University, Ziro, Arunachal Pradesh, India.

Department of Biochemistry, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh-462020, India.

出版信息

Anticancer Agents Med Chem. 2022;22(7):1257-1271. doi: 10.2174/1871520621666210712090017.

Abstract

Tissues are progressively molded by bidirectional correspondence between denizen cells and extracellular matrix (ECM) via cell-matrix connections along with ECM remodeling. The composition and association of ECM are spatiotemporally directed to control cell conduct and differentiation; however, dysregulation of ECM dynamics prompts the development of diseases, for example, cancer. Emerging information demonstrates that hypoxia may have decisive roles in metastasis. In addition, the sprawling nature of neoplastic cells and chaotic angiogenesis are increasingly influencing microcirculation as well as altering the concentration of oxygen. In various regions of the tumor microenvironment, hypoxia, an essential player in the multistep phase of cancer metastasis, is necessary. Hypoxia can be turned into an advantage for selective cancer therapy because it is much more severe in tumors than in normal tissues. Cellular matrix gives signaling cues that control cell behavior and organize cells' elements in tissue development and homeostasis. The interplay between intrinsic factors of cancer cells themselves, including their genotype and signaling networks, and extrinsic factors of tumor stroma, for example, ECM and ECM remodeling, together decide the destiny and behavior of tumor cells. Tumor matrix encourages the development, endurance, and invasion of neoplastic and immune cell activities to drive metastasis and debilitate treatment. Incipient evidence recommends essential parts of tumor ECM segments and their remodeling in controlling each progression of the cancer-immunity cycle. Scientists have discovered that tumor matrix dynamics as well as matrix remodeling in perspective to anti-tumor immune reactions are especially important for matrix-based biomarkers recognition and followed by immunotherapy and targeting specific drugs.

摘要

组织通过细胞-基质连接以及细胞外基质(ECM)重塑,在常驻细胞和细胞外基质(ECM)之间进行双向通讯,从而逐渐进行塑造。ECM 的组成和关联在时空上被指导以控制细胞行为和分化;然而,ECM 动态的失调会促使疾病的发展,例如癌症。新出现的信息表明,缺氧可能在转移中起决定性作用。此外,肿瘤细胞的蔓延性质和混乱的血管生成越来越多地影响微循环,并改变氧气浓度。在肿瘤微环境的各个区域,缺氧是癌症转移多步骤阶段的重要参与者,是必需的。缺氧可以成为癌症选择性治疗的优势,因为它在肿瘤中比在正常组织中更为严重。细胞外基质提供信号线索,控制细胞行为并组织组织发育和稳态中的细胞成分。癌细胞自身的内在因素,包括其基因型和信号网络,以及肿瘤基质的外在因素,例如细胞外基质和细胞外基质重塑,共同决定肿瘤细胞的命运和行为。肿瘤基质促进了肿瘤和免疫细胞活动的发展、维持和侵袭,以驱动转移并削弱治疗效果。初步证据表明,肿瘤 ECM 片段及其重塑在控制癌症-免疫周期的每个进展中起着至关重要的作用。科学家们已经发现,肿瘤基质动力学以及肿瘤基质重塑与抗肿瘤免疫反应之间的关系,对于基于基质的生物标志物识别以及随后的免疫疗法和靶向特定药物的治疗特别重要。

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