Human ovarian carcinoma–associated mesenchymal stem cells regulate cancer stem cells and tumorigenesis via altered BMP production

Deriving from bone marrow, the bone marrow mesenchymal stem cells (BMSCs) possess multipolar chemotaxis, proliferation potential, along with the capability to differentiate into various types of cells. Moreover, the hypoxic stimulation can effectively induce BMSCs differentiation. This study intends to explore the impediment of BMSCs on malignant behaviors of lung cancer stem cells under hypoxia. A co-culture system of BMSCs with A549 cells was established and then assigned into normoxia group, hypoxia group (50, 100, and 200 nmol/L) followed by analysis of cell viability by CCK-8 assay and miR-145 expression by qRT-PCR. In addition, A549 cells were grouped into NC group, miR-145-mimics group, and miR-145-inhibitors group followed by analysis of cell invasion and levels of miR-145 and Oct4. Hypoxia group exhibited a reduced cell viability and higher miR-145 expression (146.01±21.23%) compared to normoxia group (P < 0.05). Transfection of miR-145-mimic significantly upregulated miR-145 and decreased cell invasion (7.49±1.43%) compared with miR-145-inhibitors group or NC group (P < 0.05). Meanwhile, Oct4 level in miR-145-mimics group (0.934±2.98) was significantly decreased (P < 0.05). In conclusion, under hypoxia condition, the co-culture with BMSCs can upregulated miR-145 level, effectively reduce the viability of lung cancer stem cells and restrain proliferation capability.

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Mesenchymal Stem Cells and Cancer Stem Cells: An Overview of Tumor-Mesenchymal Stem Cell Interaction for therapeutic interventions

Current Drug Targets ◽

10.2174/1389450122666210824142247 ◽

2021 ◽

Vol 22 ◽

Author(s):

Soheila Montazersaheb ◽

Ezzatollah Fathi ◽

Ayoub Mamandi ◽

Raheleh Farahzadi ◽

Hamid Reza Heidari

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Tumor Microenvironment ◽

Cancer Stem Cells ◽

Tumor Cells ◽

Cell Types ◽

Cell Interaction ◽

Therapeutic Interventions ◽

Tumorigenic Potential ◽

Different Types

: Tumors are made up of different types of cancer cells that contribute to tumor heterogeneity. Among these cells, cancer stem cells (CSCs) have a significant role in the onset of cancer and development. Like other stem cells, CSCs are characterized by the capacity for differentiation and self-renewal. A specific population of CSCs is constituted by mesenchymal stem cells (MSCs) that differentiate into mesoderm-specific cells. The pro-or anti-tumorigenic potential of MSCs on the proliferation and development of tumor cells has been reported as contradictory results. Also, tumor progression is specified by the corresponding tumor cells like the tumor microenvironment. The tumor microenvironment consists of a network of reciprocal cell types such as endothelial cells, immune cells, MSCs, and fibroblasts as well as growth factors, chemokines, and cytokines. In this review, recent findings related to the tumor microenvironment and associated cell populations, homing of MSCs to tumor sites, and interaction of MSCs with tumor cells will be discussed.

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Human omental adipose-derived mesenchymal stem cells enhance autophagy in ovarian carcinoma cells through the STAT3 signalling pathway

Cellular Signalling ◽

10.1016/j.cellsig.2020.109549 ◽

2020 ◽

Vol 69 ◽

pp. 109549 ◽

Cited By ~ 1

Author(s):

Yijing Chu ◽

Yan Wang ◽

Kun Li ◽

Meixin Liu ◽

Yan Zhang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Ovarian Carcinoma ◽

Carcinoma Cells ◽

Signalling Pathway ◽

Ovarian Carcinoma Cells ◽

Stat3 Signalling

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Abstract 4091: Investigations on the role of epithelial-mesenchymal transition and cancer stem cells in the response to therapy in patient-derived ovarian carcinoma xenografts

10.1158/1538-7445.am2015-4091 ◽

2015 ◽

Author(s):

Francesca Ricci ◽

Federica Guffanti ◽

Maddalena Fratelli ◽

Broggini Massimo ◽

Giovanna Damia

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Ovarian Carcinoma ◽

Epithelial Mesenchymal Transition ◽

Response To Therapy ◽

Mesenchymal Transition

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Dysregulated MicroRNA Fingerprints and Methylation Patterns in Hepatocellular Carcinoma, Cancer Stem Cells, and Mesenchymal Stem Cells

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2019.00229 ◽

2019 ◽

Vol 7 ◽

Cited By ~ 6

Author(s):

Mohamed A. Nasr ◽

Radwa Ayman Salah ◽

M. Abd Elkodous ◽

Shimaa E. Elshenawy ◽

Nagwa El-Badri

Keyword(s):

Hepatocellular Carcinoma ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cancer Stem Cells ◽

Methylation Patterns

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Aldehyde dehydrogenase activity in serous ovarian carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e15577 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e15577-e15577

Author(s):

Petra M. Bareiss ◽

Tanja N. Fehm ◽

Anna Fischer ◽

Matthias Grauer ◽

Philipp Kokorsch ◽

...

Keyword(s):

Cell Cycle ◽

Stem Cells ◽

Cancer Stem Cells ◽

Ovarian Carcinoma ◽

Aldehyde Dehydrogenase ◽

Cell Cycle Distribution ◽

Aldh Activity ◽

Serous Ovarian Carcinoma ◽

Aldh1 Expression

e15577 Background: Only specific subpopulations of tumor cells, so called cancer stem cells (CSC) may initiate and maintain tumors. The phenotype and molecular properties of ovarian CSC remain elusive. Aldehyde dehydrogenase (ALDH) activity characterizes (cancer) stem cells in different tissues and has been associated with ovarian CSC (Silva et al, 2011; Kryczek et al, 2012). Contradictory results have been reported on ALDH1 expression and prognosis in ovarian carcinoma. In this study, we explore the role of ALDH in serous ovarian carcinoma (SOC). Methods: Aldefluor-staining was used to assess ALDH activity in different ovarian carcinoma cell-lines and patient samples. ALDH+ and ALDH- cells isolated by FACS and ALDH1 versus control siRNA treated cells were analyzed in sphere forming, proliferation, BrdU and cell cycle assays. In vivo tumorigenicity assays including serial re-transplantations were performed in NOD/SCID/IL2Rγnull mice. ALDH1 and Ki67 expression were assessed immunohistochemically on a tissue microarray of 152 SOC samples. Results: ALDH+ cells formed more tumor spheres than ALDH- cells from the OVCAR-3 cell line and primary SOC and larger spheres (> 5.000 µm²) developed solely from ALDH+ cells. However, in vivo both cell fractions gave rise to tumors. Tumors contained both ALDH+ and ALDH- cells irrespective of the starting population. Notably, ALDH+ cells generated tumors more rapidly and induced larger tumors, suggesting a higher proliferative capacity. Immunohistochemical analysis of a larger cohort of SOC patients confirmed association of ALDH1 expression with the proliferation marker Ki67 (p=0.007). Surprisingly, co-stainings revealed that ALDH1 positive cells were mostly Ki67 negative and cell cycle synchronisation experiments using different agents showed ALDH induction in G0-enriched OVCAR-3 cells. However, inhibition of ALDH by treatment with three distinct siRNAs against ALDH1 did not alter cell cycle distribution. Conclusions: Our data suggest that ALDH is a correlative marker indicating, but not actively sustaining a quiescent stem-cell like state in SOC. Upon exit from G0, ALDH+ cells lose ALDH expression and induce a proliferative response.

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