Dataset Information

The Interplay between Integrins and Immune Cells as a Regulator in Cancer Immunology.

ABSTRACT: Integrins are a group of heterodimers consisting of α and β subunits that mediate a variety of physiological activities of immune cells, including cell migration, adhesion, proliferation, survival, and immunotolerance. Multiple types of integrins act differently on the same immune cells, while the same integrin may exert various effects on different immune cells. In the development of cancer, integrins are involved in the regulation of cancer cell proliferation, invasion, migration, and angiogenesis; conversely, integrins promote immune cell aggregation to mediate the elimination of tumors. The important roles of integrins in cancer progression have provided valuable clues for the diagnosis and targeted treatment of cancer. Furthermore, many integrin inhibitors have been investigated in clinical trials to explore effective regimens and reduce side effects. Due to the complexity of the mechanism of integrin-mediated cancer progression, challenges remain in the research and development of cancer immunotherapies (CITs). This review enumerates the effects of integrins on four types of immune cells and the potential mechanisms involved in the progression of cancer, which will provide ideas for more optimal CIT in the future.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC10093897 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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The Interplay between Integrins and Immune Cells as a Regulator in Cancer Immunology.

Zhang Qingfang Q Zhang Shuo S Chen Jianrui J Xie Zhenzhen Z

International journal of molecular sciences 20230324 7

Integrins are a group of heterodimers consisting of α and β subunits that mediate a variety of physiological activities of immune cells, including cell migration, adhesion, proliferation, survival, and immunotolerance. Multiple types of integrins act differently on the same immune cells, while the same integrin may exert various effects on different immune cells. In the development of cancer, integrins are involved in the regulation of cancer cell proliferation, invasion, migration, and angiogen ...[more]

PMID: 37047140

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Project description:Introduction: Upon BMP-2 stimulation, the osteoblastic lineage commitment in C2C12 myoblasts is associated with a microenvironmental change that occurs over several days. How does BMP-2 operate a switch in adhesive machinery to adapt to the new microenvironment and to drive bone cell fate is not well understood. Here, we addressed this question for BMP-2 delivered either in solution or physically bound of a biomimetic film, to mimic its presentation to cells via the extracellular matrix (ECM). Methods: Biommetics films were prepared using a recently developed automated method that enable high content studies of cellular processes. Comparative gene expressions were done using RNA sequencing from the encyclopedia of the regulatory elements (ENCODE). Gene expressions of transcription factors, beta chain (1, 3, 5) integrins and cadherins (M, N, and Cad11) were studied using quantitative PCR. ECM proteins and adhesion receptor expressions were also quantified by Western blots and dot blots. Their spatial organization in and around cells was studied using immuno-stainings. The individual effect of each receptor on osteogenic transcription factors and alkaline phosphatase expression were studied using silencing RNA of each integrin and cadherin receptor. The organization of fibronectin was studied using immuno-staining and quantitative microscopic analysis. Results: Our findings highlight a switch of integrin and cadherin expression during muscle to bone transdifferentiation upon BMP-2 stimulation. This switch occurs no matter the presentation mode, for BMP-2 presented in solution or via the biomimetic film. While C2C12 muscle cells express M-cadherin and Laminin-specific integrins, the BMP-2-induced transdifferentiation into bone cells is associated with an increase in the expression of cadherin-11 and collagen-specific integrins. Biomimetic films presenting matrix-bound BMP-2 enable the revelation of specific roles of the adhesive receptors depending on the transcription factor. Discussion: While β3 integrin and cadherin-11 work in concert to control early pSMAD1,5,9 signaling, β1 integrin and Cadherin-11 control RunX2, ALP activity and fibronectin organization around the cells. In contrast, while β1 integrin is also important for osterix transcriptional activity, Cadherin-11 and β5 integrin act as negative osterix regulators. In addition, β5 integrin negatively regulates RunX2. Our results show that biomimetic films can be used to delinate the specific events associated with BMP-2-mediated muscle to bone transdifferentiation. Our study reveals how integrins and cadherins work together, while exerting distinct functions to drive osteogenic programming. Different sets of integrins and cadherins have complementary mechanical roles during the time window of this transdifferentiation.

Dataset Information

The Interplay between Integrins and Immune Cells as a Regulator in Cancer Immunology.

Publications

The Interplay between Integrins and Immune Cells as a Regulator in Cancer Immunology.

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