Administration of Cripto in <scp>GRP</scp>78 overexpressed human <scp>MSC</scp>s enhances stem cell viability and angiogenesis during human <scp>MSC</scp> transplantation therapy

Kim, S.; Yoon, Yeup; Han, Yong‐Seok; Lee, J. H.; Hur, Jin; Lee, S. H.

doi:10.1111/cpr.12463

Cited by 9 publications

(13 citation statements)

References 32 publications

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“…By using the Target Scan Human 7.2 database, we predicted that miR-138-1-3p targets CRIPTO as a downstream molecule, which was confirmed via the luciferase reporter assay and western blotting experiments, demonstrating that miR-138-1-3p can regulate the expression levels of CRIPTO. Several studies have shown that CRIPTO and GRP78 can form a complex on the cell membrane and activate the JAK2/STAT3 pathway, imparting stem cell like characteristics in the host cell with increased proliferation activity (18,31). Our immunohistochemical analysis revealed the colocalization of CRIPTO and GRP78 on the cell membrane that changed when miR-138-1-3p expression was altered.…”

Section: Discussionmentioning

confidence: 62%

MiR-138-1-3p alters the stemness and radiosensitivity of tumor cells by targeting CRIPTO and the JAK2/STAT3 pathway in nasopharyngeal carcinoma

Jiang

Chen

et al. 2021

Ann Transl Med

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Background: Tumor resistance to radiotherapy is one of the main obstacles to the clinical treatment of nasopharyngeal carcinoma (NPC). Improving the radiosensitivity of tumor cells has an important clinical significance in treatment of clinical NPC. This study aimed to identify that miR-138-1-3p as a novel therapeutic target in radioresistant NPC cells and found its targets, CRIPTO and the JAK2/STAT3 pathway.Methods: Radioresistant C666-IR and HK-1R cells were derived from the NPC cell lines C666-1 and HK-1. The different microRNAs (miRNAs) and their targeting genes were analyzed between C666-1 and C666-IR cells using microarray bioinformatics. Western blot, qRT-PCR, gene transfection, Luciferase reporter assay, and confocal laser scanning microscopy were applied for the analysis of the different genes.Results: MiR-138-1-3p was found to target CRIPTO, which involved in the epithelial-mesenchymal transition (EMT) and JAK2/STAT3 signaling pathways. The luciferase reporter assay confirmed that miR-138-1-3p targeted CRIPTO and downregulated the expression of CRIPTO. Furthermore, miR-138-1-3p affected the stability of the CRIPTO-GRP78 complex on the cell membrane and also reversed the radioresistant characteristics of NPC stem cells, which affected EMT and the JAK2/STAT3 signaling pathway. Conclusions:The miR-138-1-3p is a small molecule that can modulate radiosensitivity in the radioresistant C666-IR and HK-1R NPC cell lines by inhibiting EMT and targeting CRIPTO to reduce the activation of the JAK2/STAT3 pathway.

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Section: Discussionmentioning

confidence: 62%

MiR-138-1-3p alters the stemness and radiosensitivity of tumor cells by targeting CRIPTO and the JAK2/STAT3 pathway in nasopharyngeal carcinoma

Jiang

Chen

et al. 2021

Ann Transl Med

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“…Studies have demonstrated that, in response to tissue damage signals, MSCs release paracrine/endocrine factors that help control inflammation and stimulate tissue regeneration by endogenous mechanisms [ 55 ]. The recognition of these immunomodulatory/trophic actions with beneficial effects and migratory capacity in different tissues makes MSCs a unique therapeutic strategy [ 56 , 57 ]. These MSC characteristics have also led their original describer, Caplan, to call for a further nomenclature change to medicinal signaling cells [ 53 ].…”

Section: Mesenchymal Stromal Cellsmentioning

confidence: 99%

Is there a place for mesenchymal stromal cell-based therapies in the therapeutic armamentarium against COVID-19?

et al. 2021

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The COVID-19 pandemic, caused by the rapid global spread of the novel coronavirus (SARS-CoV-2), has caused healthcare systems to collapse and led to hundreds of thousands of deaths. The clinical spectrum of COVID-19 is not only limited to local pneumonia but also represents multiple organ involvement, with potential for systemic complications. One year after the pandemic, pathophysiological knowledge has evolved, and many therapeutic advances have occurred, but mortality rates are still elevated in severe/critical COVID-19 cases. Mesenchymal stromal cells (MSCs) can exert immunomodulatory, antiviral, and pro-regenerative paracrine/endocrine actions and are therefore promising candidates for MSC-based therapies. In this review, we discuss the rationale for MSC-based therapies based on currently available preclinical and clinical evidence of safety, potential efficacy, and mechanisms of action. Finally, we present a critical analysis of the risks, limitations, challenges, and opportunities that place MSC-based products as a therapeutic strategy that may complement the current arsenal against COVID-19 and reduce the pandemic’s unmet medical needs.

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“…Blocking CRIPTO also drives dopaminergic neuron over astrocyte differentiation during neural differentiation from embryonic stem cells, thus implicating CRIPTO in control of neural stem cells and lineage fate decisions and making it an important consideration in the development of bioscaffold based stem cell transplantation approaches for neural regeneration following injury [ 81 , 82 ]. In a hindlimb ischemic model, CRIPTO was shown to interact with the concomitantly induced and overexpressed GRP78 and to synergistically increase human mesenchymal stem cell (MSC) proliferation, migration and invasion potential with potential applications for MSC-based transplantation and regeneration approaches for treating wounds [ 83 ]. There is an interesting parallel here between the hypoxic microenvironment associated with this ischemia model and the role of hypoxia in CRIPTO-mediated hematopoietic stem cell maintenance, however here as exactly how stress signals are integrated across multiple cell types has not been investigated thoroughly, and, although CRIPTO is a known Hif1 α target [ 84 ], it remains to be determined if Hif1 α is required for all adaptive responses that go through CRIPTO.…”

Section: Rise and Fall Of Criptomentioning

confidence: 99%

“…Furthermore, hypoxic conditions within these tumor regions may also influence local CRIPTO production as a function of HIF1α binding to hypoxia response elements (HREs) within the CRIPTO promoter [ 84 ]. This harkens to the integration of hypoxic stress and CRIPTO signaling in HSCs, ischemia models and cardiomyocytes [ 39 , 83 , 84 ]. Alternatively, these zones are likely starved for other nutrients and, in this regard, we found that nutrient deprivation in vitro (i.e., serum withdrawal or glycolytic blockade) confers cancer cell CRIPTO dependency [ 118 ].…”

Section: Re-emergence Of Criptomentioning

confidence: 99%

Whence CRIPTO: The Reemergence of an Oncofetal Factor in ‘Wounds’ That Fail to Heal

Freeman

Sousa

Karkampouna

et al. 2021

IJMS

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There exists a set of factors termed oncofetal proteins that play key roles in ontogeny before they decline or disappear as the organism’s tissues achieve homeostasis, only to then re-emerge in cancer. Although the unique therapeutic potential presented by such factors has been recognized for more than a century, their clinical utility has yet to be fully realized1. This review highlights the small signaling protein CRIPTO encoded by the tumor derived growth factor 1 (TDGF1/Tdgf1) gene, an oft cited oncofetal protein whose presence in the cancer literature as a tumor promoter, diagnostic marker and viable therapeutic target continues to grow. We touch lightly on features well established and well-reviewed since its discovery more than 30 years ago, including CRIPTO’s early developmental roles and modulation of SMAD2/3 activation by a selected set of transforming growth factor β (TGF-β) family ligands. We predominantly focus instead on more recent and less well understood additions to the CRIPTO signaling repertoire, on its potential upstream regulators and on new conceptual ground for understanding its mode of action in the multicellular and often stressful contexts of neoplastic transformation and progression. We ask whence it re-emerges in cancer and where it ‘hides’ between the time of its fetal activity and its oncogenic reemergence. In this regard, we examine CRIPTO’s restriction to rare cells in the adult, its potential for paracrine crosstalk, and its emerging role in inflammation and tissue regeneration—roles it may reprise in tumorigenesis, acting on subsets of tumor cells to foster cancer initiation and progression. We also consider critical gaps in knowledge and resources that stand between the recent, exciting momentum in the CRIPTO field and highly actionable CRIPTO manipulation for cancer therapy and beyond.

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Administration of Cripto in GRP78 overexpressed human MSCs enhances stem cell viability and angiogenesis during human MSC transplantation therapy

Cited by 9 publications

References 32 publications

MiR-138-1-3p alters the stemness and radiosensitivity of tumor cells by targeting CRIPTO and the JAK2/STAT3 pathway in nasopharyngeal carcinoma

MiR-138-1-3p alters the stemness and radiosensitivity of tumor cells by targeting CRIPTO and the JAK2/STAT3 pathway in nasopharyngeal carcinoma

Is there a place for mesenchymal stromal cell-based therapies in the therapeutic armamentarium against COVID-19?

Whence CRIPTO: The Reemergence of an Oncofetal Factor in ‘Wounds’ That Fail to Heal

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