Suppression of tumor cell proliferation and migration by human umbilical cord mesenchymal stem cells: A possible role for apoptosis and Wnt signaling

Yin, Yuan; Zhou, Chang; Chen, Xuan; Tao, Changli; Cheng, Huiqing; Lu, Xiaoxuan

doi:10.3892/ol.2018.8368

Cited by 37 publications

(49 citation statements)

References 38 publications

(44 reference statements)

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“…Our data are consistent with a published study showing the anti-proliferative and apoptotic effect of human umbilical cord mesenchymal stem cells (hUCMSCs) conditioned medium (22). An increase in the percentage of BxPC-3 cells exhibiting increased levels of ROS upon incubation with CCs conditioned medium was observed as suggested by others (23,24).…”

Section: Discussionsupporting

confidence: 93%

Cumulus Cells Are Potential Candidates for Cell Therapy

Mohammed

Yılmaz

Akçin

et al. 2019

In Vivo

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Background/Aim: Cumulus cells (CCs) originate from the membrane granulosa cells and surround oocytes during follicle maturation. CCs produce high levels of hyaluronan that targets CD44, which is a major tumorigenic marker. This study aimed to investigate whether CCs have a role in cell therapy by targeting CD44 in pancreatic cancer cells. Materials and Methods: CCs were isolated from the oocytes and incubated in a hypoxic environment. BxPC-3 pancreatic cancer cells were treated with CC conditioned media for three days. Results: Conditioned media of CC cells incubated in hypoxic conditions caused a 25% reduction in the viability of BxPC-3 cells. Expression of anti-apoptotic genes was down-regulated, while that of pro-apoptotic genes was upregulated. An increased number of BxPC-3 cells exhibited increased levels of reactive oxygen species and arrested in the synthesis (S) phase of the cell cycle. Conclusion: CCs conditioned medium induced apoptosis of pancreatic cancer cells. Cumulus cells (CCs) are a specialized group of granulosa cells, which are in intimate contact with oocytes (1, 2) both in the ovarian follicle and after ovulation. CCs are removed in routine human intra-cytoplasmic sperm injection (ICSI) practices for better capturing of the polar body. CCs play an essential role in regulating oocyte maturation (3, 4); they surround the mature oocyte and give rise to a cumulus mass of several millimeters (5). Several studies on CCs have focused on their role in oocyte maturation and fertilization and on their use as novel non-invasive diagnostic biomarkers to determine oocyte quality (6). Many types of cancers are characterized by elevated levels of reactive oxygen species (ROS), which play an essential role in cell proliferation, differentiation, and cell survival (7). CCs have a protective effect against ROS, but only to a certain extent. The process of CC expansion requires the production of hyaluronic acid (8, 9), which is the primary CD44 binding molecule overexpressed in many solid tumors, such as pancreatic cancer (10). CD44 is a non-kinase transmembrane glycoprotein, which has been shown to be overexpressed in a variety of cells such as cancer stem cells and mutations in this gene are thought to play a role in tumorigenesis (11). Targeting this protein through CCs might have an anti-carcinogenic effect on pancreatic cancer cells. Materials and Methods Tissue collection and sample preparation. The tissue of origin of CCs was obtained from the IVF lab. Tissues were minced in phosphate buffered saline (PBS) by pipetting vigorously and transferred into T25 flasks coated with Type I Collagen (STEMCELL Technologies, Kent, WA, USA). CCs were cultured in RPMI-1640 (Life Technologies, Grand Island, NY, USA), supplemented with 10% FBS (Life Technologies) and 1% penicillin/streptomycin/amphotericin (PSA) Life Technologies), and incubated in hypoxic conditions (2% O 2). Floating tissues and cells flask were discarded and the medium was replaced with fresh medium and left in the incubator for three to four days. Co...

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Section: Discussionsupporting

confidence: 93%

Cumulus Cells Are Potential Candidates for Cell Therapy

Mohammed

Yılmaz

Akçin

et al. 2019

In Vivo

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“…Hence, we contend that exosomal miR-375 may suppress ESCC by inactivating the Bcl-2 signaling pathway, which has been previously identified in colon cancer [ 40 ]. Additionally, hUCMSCs have the ability to suppress the initiation and development of lung cancer and hepatocellular cancer, highlighting that hUCMSCs can exert broad tumor-suppressive effects [ 41 ]. Moreover, hUCMSCs-exo impairs the development of pancreatic ductal adenocarcinoma through delivery of exogenous miR-145-5p [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

Human umbilical cord mesenchymal stem cells-derived exosomes deliver microRNA-375 to downregulate ENAH and thus retard esophageal squamous cell carcinoma progression

Zheng

et al. 2020

J Exp Clin Cancer Res

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Background: Exosomal microRNAs (miRNAs or miRs) from bone marrow-derived mesenchymal stem cells (UCMSCs) have emerged as promising therapeutic strategies for cancer treatment. The current study aimed to elucidate the underlying mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs)-derived exosomal miR-375 in esophageal squamous cell carcinoma (ESCC). Methods: After determining the expression of miR-375 and its putative target enabled homolog (ENAH) in ESCC tissues and cells, we tested effects of their altered expression on ESCC proliferation, invasion, migration, and tumorsphere formation was subsequently measured. Transfected hUCMSCs-derived exosomes (hUCMSCs-exo) were isolated and co-cultured with ESCC cells to measure the effects of miR-375 delivered by hUCMSCs-exo on ESCC development. Finally, we investigated the effect of miR-375 on tumor growth in vivo. Results: The expression of miR-375 was reduced, while the expression of ENAH was elevated in ESCC. ENAH was identified as a target gene of miR-375. Elevated miR-375 or depleted ENAH expression inhibited ESCC cell proliferation, invasion, migration, tumorsphere formation, and promoted apoptosis. Moreover, miR-375 delivered by hUCMSCs-exo could suppress ESCC cell proliferation, invasion, migration, tumorsphere formation, but promoted apoptosis in vitro, as well as inhibiting tumor growth in vivo. Conclusions: Taken together, hUCMSCs-exo can deliver miR-375 to suppress ENAH expression and subsequently inhibit the initiation and progression of ESCC.

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“…Furthermore, ADMSCs support breast tumor growth and progression[42] but can inhibit proliferation of pancreatic cancer cells in vitro and in vivo [40]. MSCs can also inhibit tumor growth in Kaposi’s sarcoma[43], colon cancer[44,45], hepatoma[46,47], prostate[48,49], pancreatic[50,51], lung cancer[47] and other tumor models[52]. Similar controversies were reported concerning the effect of the SC secretome.…”

Section: Discussionmentioning

confidence: 99%

Effect of adipose-derived mesenchymal stem cells on hepatocellular carcinoma: In vitro inhibition of carcinogenesis

Serhal

Saliba

Hilal

et al. 2019

WJG

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AIM To investigate the effect of adipose-derived mesenchymal stem cells (ADMSCs) and their conditioned media (CM) on hepatocellular carcinoma (HCC) cell tumorigenesis. METHODS The proliferation rate of HepG2 and PLC-PRF-5 HCC cancer cells was measured using the trypan blue exclusion method and confirmed using the cell-counting kit 8 (commonly known as CCK-8) assay. Apoptosis was detected by flow cytometry using annexin V-FITC. Protein and mRNA expression was quantified by ELISA and real time PCR, respectively. Migration and invasion rates were performed by Transwell migration and invasion assays. Wound healing was examined to confirm the data obtained from the migration assays. RESULTS Our data demonstrated that when co-culturing HCC cell lines with ADMSCs or treating them with ADMSC CM, the HCC cell proliferation rate was significantly inhibited and the apoptosis rate increased. The decreased proliferation rate was accompanied by an upregulation of P53 and Retinoblastoma mRNA and a downregulation of c-Myc and hTERT mRNA levels. More notably, ADMSCs and their CM suppressed the expression of the two important markers of HCC carcinogenicity, alpha-fetoprotein and Des-gamma-carboxyprothrombin. In addition, the migration and invasion levels of HepG2 and PLC-PRF-5 cells significantly decreased, potentially through increased expression of the tissue inhibitor metalloproteinases TIMP-1, TIMP-2 and TIMP-3. CONCLUSION These findings shed new light on a protective and therapeutic role for ADMSCs and their CM in controlling HCC invasiveness and carcinogenesis.

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Suppression of tumor cell proliferation and migration by human umbilical cord mesenchymal stem cells: A possible role for apoptosis and Wnt signaling

Cited by 37 publications

References 38 publications

Cumulus Cells Are Potential Candidates for Cell Therapy

Cumulus Cells Are Potential Candidates for Cell Therapy

Human umbilical cord mesenchymal stem cells-derived exosomes deliver microRNA-375 to downregulate ENAH and thus retard esophageal squamous cell carcinoma progression

Effect of adipose-derived mesenchymal stem cells on hepatocellular carcinoma: In vitro inhibition of carcinogenesis

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