Exosomes from Human Omental Adipose-Derived Mesenchymal Stem Cells Secreted into Ascites Promote Peritoneal Metastasis of Epithelial Ovarian Cancer

Qu, Qingxi; Liu, Linghong; Cui, Yingying; Chen, Yu; Wang, Yu; Wang, Yaodu

doi:10.3390/cells11213392

Cited by 16 publications

(6 citation statements)

References 36 publications

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“…Moreover, the TCGA data set displayed that the expression of KIF20A and CCNE2 was markedly augmented in NSCLC tissues. Abnormal KIF20A might induce aberrant cell division in cancer, thereby leading to KIF20A as a promising predictive and prognostic marker in pancreatic cancer, epithelial ovarian cancer, and lung adenocarcinoma patients (Qu et al, 2022; J. Zhang et al, 2022; X. Zhao et al, 2018). Moreover, high expression of CCNE2 was also reported in various tumors.…”

Section: Discussionmentioning

confidence: 99%

Berberine targets KIF20A and CCNE2 to inhibit the progression of nonsmall cell lung cancer via the PI3K/AKT pathway

Wang

Hua

et al. 2023

Drug Development Research

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BackgroundNonsmall cell lung cancer (NSCLC) is the main type of lung cancer, accounting for approximately 85%. Berberine (BBR), a commonly used traditional Chinese medicine, has been reported to exhibit a potential antitumor effect in various cancers. In this research, we explored the function of BBR and its underlying mechanisms in the development of NSCLC.MethodsCell Counting Kit‐8 (CCK‐8), 5‐ethynyl‐20‐deoxyuridine (EdU), colony formation assays, flow cytometry, and transwell invasion assay were employed to determine cell growth, the apoptotic rate, cell invasion of NSCLC cells, respectively. Western blot was applied for detecting the protein expression of c‐Myc, matrix metalloprotease 9 (MMP9), kinesin family member 20A (KIF20A), cyclin E2 (CCNE2), and phosphatidylinositol‐3‐kinase/protein kinase B (PI3K/AKT) pathway‐related proteins. Glycolysis was evaluated by detecting glucose consumption, lactate production, and adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio with the matched kits. Real‐time quantitative polymerase chain reaction (RT‐qPCR) was conducted to analyze the level of KIF20A and CCNE2. Tumor model was established to evaluate the function of BBR on tumor growth in NSCLC in vivo. In addition, immunohistochemistry assay was employed to detect the level of KIF20A, CCNE2, c‐Myc, and MMP9 in mice tissues.ResultsBBR exhibited suppressive effects on the progression of NSCLC, as evidenced by inhibiting cell growth, invasion, glycolysis, and facilitating cell apoptosis in H1299 and A549 cells. KIF20A and CCNE2 were upregulated in NSCLC tissues and cells. Moreover, BBR treatment significantly decreased the expression of KIF20A and CCNE2. KIF20A or CCNE2 downregulation could repress cell proliferation, invasion, glycolysis, and induce cell apoptosis in both H1299 and A549 cells. The inhibition effects of BBR treatment on cell proliferation, invasion, glycolysis, and promotion effect on cell apoptosis were rescued by KIF20A or CCNE2 overexpression in NSCLC cells. The inactivation of PI3K/AKT pathway caused by BBR treatment in H1299 and A549 cells was restored by KIF20A or CCNE2 upregulation. In vivo experiments also demonstrated that BBR treatment could repress tumor growth by regulating KIF20A and CCNE2 and inactivating the PI3K/AKT pathway.ConclusionBBR treatment showed the suppressive impact on the progression of NSCLC by targeting KIF20A and CCNE2, thereby inhibiting the activation of the PI3K/AKT pathway.

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Section: Discussionmentioning

confidence: 99%

Berberine targets KIF20A and CCNE2 to inhibit the progression of nonsmall cell lung cancer via the PI3K/AKT pathway

Wang

Hua

et al. 2023

Drug Development Research

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“…In another study, the coculture of human omental AD‐MSCs with OC cells increased the growth, invasion, and migration of cancer cells. Plus, the exosomes secreted by human omental AD‐MSCs promoted OC cell activity by influencing FOXM1, MAPK, KIF20A, and Cyclin F signaling pathways in vitro and potentiated OC growth and metastasis in vivo 81 . Another mechanism of AD‐MSCs for promoting OC cells is triggering STAT3 signaling pathway enhancing autophagy.…”

Section: Adipose Tissue Mscs and Ocmentioning

confidence: 98%

Mesenchymal stem cells and ovarian cancer: Is there promising news?

Jahani,

Zare,

Mirzaei

et al. 2023

J of Cellular Biochemistry

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Ovarian cancer (OC) is described as a heterogeneous complex condition with high mortality, weak prognosis, and late‐stage presentation. OC has several subgroups based on different indices, like the origin and histopathology. The current treatments against OC include surgery followed by chemotherapy and radiotherapy; however, these methods have represented diverse side effects without enough effectiveness on OC. Recently, mesenchymal stem cell (MSC)‐based therapy has acquired particular attention for treating diverse problems, such as cancer. These multipotent stem cells can be obtained from different sources, such as the umbilical cord, adipose tissues, bone marrow, and placenta, and their efficacy has been investigated against OC. Hence, in this narrative review, we aimed to review and discuss the present studies about the effects of various sources of MSCs on OC with a special focus on involved mechanisms.

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“…For instance, adipocyte-derived exosomes originating from breast cancers drive lung metastases [ 115 ], while those from epithelial ovarian cancers facilitate peritoneal metastases. These exosomes are released by mature adipocytes harboring mesenchymal stem cell (MSC)-like characteristics [ 116 ]. It is now accepted that MSC-derived exosomes can switch the phenotype of stromal or normal cells to a malignant one by delivering their cargo (nucleic acids and proteins) into recipient cells (including fibroblasts, endothelial cells, epithelial cells and infiltrating leukocytes) [ 117 ].…”

Section: Cell-free Dna (Cfdna)mentioning

confidence: 99%

Tumor-derived cell-free DNA and circulating tumor cells: partners or rivals in metastasis formation?

Witz,

Dardare,

Betz

et al. 2024

Clin Exp Med

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The origin of metastases is a topic that has sparked controversy. Despite recent advancements, metastatic disease continues to pose challenges. The first admitted model of how metastases develop revolves around cells breaking away from the primary tumor, known as circulating tumor cells (CTCs). These cells survive while circulating through the bloodstream and subsequently establish themselves in secondary organs, a process often referred to as the “metastatic cascade”. This intricate and dynamic process involves various steps, but all the mechanisms behind metastatic dissemination are not yet comprehensively elucidated. The “seed and soil” theory has shed light on the phenomenon of metastatic organotropism and the existence of pre-metastatic niches. It is now established that these niches can be primed by factors secreted by the primary tumor before the arrival of CTCs. In particular, exosomes have been identified as important contributors to this priming. Another concept then emerged, i.e. the “genometastasis” theory, which challenged all other postulates. It emphasizes the intriguing but promising role of cell-free DNA (cfDNA) in metastasis formation through oncogenic formation of recipient cells. However, it cannot be ruled out that all these theories are intertwined. This review outlines the primary theories regarding the metastases formation that involve CTCs, and depicts cfDNA, a potential second player in the metastasis formation. We discuss the potential interrelationships between CTCs and cfDNA, and propose both in vitro and in vivo experimental strategies to explore all plausible theories.

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Exosomes from Human Omental Adipose-Derived Mesenchymal Stem Cells Secreted into Ascites Promote Peritoneal Metastasis of Epithelial Ovarian Cancer

Cited by 16 publications

References 36 publications

Berberine targets KIF20A and CCNE2 to inhibit the progression of nonsmall cell lung cancer via the PI3K/AKT pathway

Berberine targets KIF20A and CCNE2 to inhibit the progression of nonsmall cell lung cancer via the PI3K/AKT pathway

Mesenchymal stem cells and ovarian cancer: Is there promising news?

Tumor-derived cell-free DNA and circulating tumor cells: partners or rivals in metastasis formation?

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