CD97 promotes gastric cancer cell proliferation and invasion through exosome-mediated MAPK signaling pathway

Li, Chao; Liu, Daren; Li, Guogang; Wang, Houhong; Li, Xiaowen; Zhang, Wei; Wu, Yulian; Chen, Li

doi:10.3748/wjg.v21.i20.6215

Cited by 99 publications

(85 citation statements)

References 39 publications

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“…MSC derived exosomes have been shown to promote vascularization via the P38 mitogen activated protein kinase (MAPK) pathway [45]. Additionally, published studies have shown that this pathway is triggered during exosome mediated cell proliferation albeit in cancer cells [46]. We therefore evaluated if the pulp cell derived exosomes triggered the MAPK pathway in DPSCs upon endocytosis.…”

Section: Resultsmentioning

confidence: 99%

Exosomes as biomimetic tools for stem cell differentiation: Applications in dental pulp tissue regeneration

et al. 2016

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Achieving and maintaining safe and reliable lineage specific differentiation of stem cells is important for clinical translation of tissue engineering strategies. In an effort to circumvent the multitude of problems arising from the usage of growth factors and growth factor delivery systems, we have explored the use of exosomes as biomimetic tools to induce stem cell differentiation. Working on the hypothesis that cell-type specific exosomes can trigger lineage-specific differentiation of stem cells, we have evaluated the potential of exosomes derived from dental pulp cells cultured on under growth and odontogenic differentiation conditions to induce odontogenic differentiation of naïve human dental pulp stem cells (DPSCs) and human bone marrow derived stromal cells (HMSCs) in vitro and in vivo. Results indicate that the exosomes can bind to matrix proteins such as type I collagen and fibronectin enabling them to be tethered to biomaterials. The exosomes are endocytosed by both DPSCs and HMSCs in a dose-dependent and saturable manner via the caveolar endocytic mechanism and trigger the P38 mitogen activated protein kinase (MAPK) pathway. In addition, the exosomes also trigger the increased expression of genes required for odontogenic differentiation. When tested in vivo in a tooth root slice model with DPSCs, the exosomes triggered regeneration of dental pulp-like tissue. However, our results indicate that exosomes isolated under odontogenic conditions are better inducers of stem cell differentiation and tissue regeneration. Overall, our results highlight the potential exosomes as biomimetic tools to induce lineage specific differentiation of stem cells. Our results also show the importance of considering the source and state of exosome donor cells before a choice is made for therapeutic applications.

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Section: Resultsmentioning

confidence: 99%

Exosomes as biomimetic tools for stem cell differentiation: Applications in dental pulp tissue regeneration

et al. 2016

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“…Identification of the endocytic mechanism can provide valuable information to target EVs for therapeutic delivery. With respect to EV endocytosis, the clathrin pathway, caveolar pathway, phagocytosis, and even macropinocytosis have all been implicated in endocytosis of EVs (Mulcahy et al, 2014;Li et al, 2015;Alcayaga-Miranda et al, 2016). We observed energy dependence, dose dependence as well as dependence on membrane cholesterol indicating the involvement of the lipid raft/caveolar endocytic pathway.…”

Section: Discussionmentioning

confidence: 62%

Evaluating the Endocytosis and Lineage-Specification Properties of Mesenchymal Stem Cell Derived Extracellular Vesicles for Targeted Therapeutic Applications

et al. 2020

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Mesenchymal stem cells (MSCs) are multipotent cells with regenerative and immunomodulatory properties. Several aspects of MSC function have been attributed to the paracrine effects of MSC derived extracellular vesicles (EVs). Although MSC EVs show great promise for regenerative medicine applications, insights into their uptake mechanisms by different target cells and the ability to control MSC EV properties for defined function in vivo have remained elusive knowledge gaps. The primary goal of this study is to elucidate how the basic properties of MSC derived EVs can be exploited for function-specific activity in regenerative medicine. Our first important observation is that, MSC EVs possess a common mechanism of endocytosis across multiple cell types. Second, altering the MSC state by inducing differentiation into multiple lineages did not affect the exosomal properties or endocytosis but triggered the expression of lineagespecific genes and proteins in vitro and in vivo respectively. Overall, the results presented in this study show a common mechanism of endocytosis for MSC EVs across different cell types and the feasibility to generate functionally enhanced EVs by modifications to parental MSCs.

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“…CD97 has been shown to heterodimerize with the lysophosphatidic acid (LPA) receptor to amplify LPA‐initiated RHO‐dependent signalling and invasion in prostate cancer cells . CD97 has been shown to promote gastric cancer cell proliferation and invasion in vitro through exosome‐mediated MAPK signalling pathway . Furthermore, CD97 promoted tumour aggressiveness through the traditional G protein–coupled receptor‐mediated signalling in hepatocellular carcinoma …”

Section: Discussionmentioning

confidence: 99%

Role of CD97 small isoform in human cervical carcinoma

Feng

et al. 2019

Int J Experimental Path

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Summary Various studies revealed that elevated expression of CD97 in carcinomas is associated with the dedifferentiation, aggressiveness and metastasis of tumour. CD97 is a protein member of the epidermal growth factor seven‐transmembrane (EGF‐TM7) family of class II TM7 receptors. Our previous study suggested that the overexpression of CD97 in cervical cancer was correlated with the aggressiveness of the tumour and that CD97 might be an independent poor prognostic factor for cervical cancer patients. Based on these data, we have investigated the role of CD97 small isoform in cervical cancer proliferation, migration and invasion in vitro. Three cervical cancer cell lines were tested and the CD97 small isoform was found to be expressed predominantly in the SiHa cells. The mobile and invasive ability of different cervical cancer cell lines was not correlated positively with total CD97 protein expression but was with the level of the CD97 small isoform. Functional significance was assessed 48 hours after transient knockdown using siRNA targeting CD97 small isoform (CD97/EGF1,2,5) or a scrambled control sequence in cervical cancer cell lines. As a result, decreased ability of migration and invasion was found in CD97 small isoform RNAi cells, which showed, however, no change in cell proliferation. This study shed light on the role of the CD97 small isoform in tumour progression and provides a basis for further studies to determine its function in vivo.

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CD97 promotes gastric cancer cell proliferation and invasion through exosome-mediated MAPK signaling pathway

Abstract: CD97 promotes gastric cancer cell proliferation and invasion in vitro through exosome-mediated MAPK signaling pathway, and exosomal miRNAs are probably involved in activation of the CD97-associated pathway.

Cited by 99 publications

References 39 publications

Exosomes as biomimetic tools for stem cell differentiation: Applications in dental pulp tissue regeneration

Exosomes as biomimetic tools for stem cell differentiation: Applications in dental pulp tissue regeneration

Evaluating the Endocytosis and Lineage-Specification Properties of Mesenchymal Stem Cell Derived Extracellular Vesicles for Targeted Therapeutic Applications

Role of CD97 small isoform in human cervical carcinoma

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