Mesenchymal stem cell's secretome promotes selective enrichment of cancer stem-like cells with specific cytogenetic profile

Jiménez, Gema; Hackenberg, Michael; Catalina, Purificación; Boulaiz, Houría; Griñán‐Lisón, Carmen; García, María Ángel; Perán, Macarena; López‐Ruiz, Elena; Ramírez, Alberto; Morata-Tarifa, Cynthia; Carrasco, Esther; Aguilera, Margarita; Marchal, Juan Antonio

doi:10.1016/j.canlet.2018.04.042

Cited by 31 publications

(30 citation statements)

References 45 publications

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“…Mesenchymal stem cells perform key functions in the development of cancer including regulation of inflammatory processes, angiogenesis, metastasis, maintenance of CSCs and tumor growth [50,51]. For this reason, MSCs are recruited into the tumor niche by CSCs and interact with each other through a wide network of cytokines [52] ( Fig.…”

Section: Mesenchymal Stem Cells (Mscs)mentioning

confidence: 99%

Cancer stem cell secretome in the tumor microenvironment: a key point for an effective personalized cancer treatment

et al. 2020

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Cancer stem cells (CSCs) represent a tumor subpopulation responsible for tumor metastasis and resistance to chemo- and radiotherapy, ultimately leading to tumor relapse. As a consequence, the detection and eradication of this cell subpopulation represent a current challenge in oncology medicine. CSC phenotype is dependent on the tumor microenvironment (TME), which involves stem and differentiated tumor cells, as well as different cell types, such as mesenchymal stem cells, endothelial cells, fibroblasts and cells of the immune system, in addition to the extracellular matrix (ECM), different in composition to the ECM in healthy tissues. CSCs regulate multiple cancer hallmarks through the interaction with cells and ECM in their environment by secreting extracellular vesicles including exosomes, and soluble factors such as interleukins, cytokines, growth factors and other metabolites to the TME. Through these factors, CSCs generate and activate their own tumor niche by recruiting stromal cells and modulate angiogenesis, metastasis, resistance to antitumor treatments and their own maintenance by the secretion of different factors such as IL-6, VEGF and TGF-ß. Due to the strong influence of the CSC secretome on disease development, the new antitumor therapies focus on targeting these communication networks to eradicate the tumor and prevent metastasis, tumor relapse and drug resistance. This review summarizes for the first time the main components of the CSC secretome and how they mediate different tumor processes. Lastly, the relevance of the CSC secretome in the development of more precise and personalized antitumor therapies is discussed.

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Section: Mesenchymal Stem Cells (Mscs)mentioning

confidence: 99%

Cancer stem cell secretome in the tumor microenvironment: a key point for an effective personalized cancer treatment

et al. 2020

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“…In the last decade, various strategies based on conventional 2D cell culture platforms have been implemented to develop methods for CSC enrichment, including density gradient centrifugation [ 73 ]; hypoxia culture [ 22 , 74 ]; chemoradiotherapy stimulation [ 23 , 75 , 76 , 77 ]; side population sorting [ 78 , 79 ]; mesenchymal stem cell secretome cultures [ 80 , 81 ]; and molecule-mediated triggering, such as neural stimulating factor [ 82 ], estrogen [ 83 ], progestin [ 84 ], hypoxia-inducible factor (HIF)-1 [ 85 ], E-cadherin [ 86 ], keratin [ 87 ], poly ADP ribose polymerase (PARP) inhibitors [ 88 ], and hepatocyte growth factor (HGF)/mesenchymal-epithelial transition (c-Met) [ 89 ]. Overall, however, 2D culture conditions provide limited expansion, and the cells tend to lose clonal and differentiation capacity upon long-term passaging.…”

Section: Discussionmentioning

confidence: 99%

A Marine Collagen-Based Biomimetic Hydrogel Recapitulates Cancer Stem Cell Niche and Enhances Progression and Chemoresistance in Human Ovarian Cancer

Moon

Hwang

et al. 2020

Marine Drugs

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Recent attention has focused on the development of an effective three-dimensional (3D) cell culture system enabling the rapid enrichment of cancer stem cells (CSCs) that are resistant to therapies and serving as a useful in vitro tumor model that accurately reflects in vivo behaviors of cancer cells. Presently, an effective 3D in vitro model of ovarian cancer (OC) was developed using a marine collagen-based hydrogel. Advantages of the model include simplicity, efficiency, bioactivity, and low cost. Remarkably, OC cells grown in this hydrogel exhibited biochemical and physiological features, including (1) enhanced cell proliferation, migration and invasion, colony formation, and chemoresistance; (2) suppressed apoptosis with altered expression levels of apoptosis-regulating molecules; (3) upregulated expression of crucial multidrug resistance-related genes; (4) accentuated expression of key molecules associated with malignant progression, such as epithelial–mesenchymal transition transcription factors, Notch, and pluripotency biomarkers; and (5) robust enrichment of ovarian CSCs. The findings indicate the potential of our 3D in vitro OC model as an in vitro research platform to study OC and ovarian CSC biology and to screen novel therapies targeting OC and ovarian CSCs.

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“…This cell line is hipotriploid (complex karyotype with multiple numerical and structural chromosome abnormalities), MelA positive, p53 positive and S100 positive, and has high tumorigenic ability. Mel1 adherent cells were maintained in standard culture conditions Enriched Mel1 CSC subpopulations were obtained after culturing as primary and secondary spheroids in serum-free medium and in anchorage-independent conditions [28]. Mel1 adherent cells were cultured in a humid incubator at 37°C and 5% CO 2 , with DMEM (Dubelcco's Modified Eagle's medium) (Sigma-Aldrich, St. Louis, MO, USA) supplemented with 10% heat inactivated fetal bovine serum (FBS) (Gibco, Grand Island, NY, USA) and 1% Penicillin/Streptomycin (P/S) (Sigma-Aldrich) in 75 cm 2 flask culture (Nunc, Roskilde, Denmark), unless otherwise indicated.…”

Section: Cell Culture and Csc Enrichmentmentioning

confidence: 99%

“…For the enrichment of melanoma CSCs, we used a primary patient-derived tumour cell line (Mel1) from an MM skin biopsy (stage M1a). We studied the anchorage-independent growth of Mel1 spheres in serum-free conditions [28] to determine their CSC characteristic phenotype by determining sphere forming ability, proliferation rate of primary and secondary melanospheres, clonogenic capacity by colony-formation assay in soft agar, side population, CD20 and CD44 cell surface markers expression and ALDH activity ( Figure 1). Figure 1A, C-E).…”

Section: Characterization Of Primary Mel1 Melanospheresmentioning

confidence: 99%

Metabolomic profile of cancer stem cell‐derived exosomes from patients with malignant melanoma

et al. 2020

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Malignant melanoma (MM) is the most aggressive and life-threatening form of skin cancer. It is characterized by an extraordinary metastasis capacity and chemotherapy resistance, mainly due to melanoma cancer stem cells (CSCs). To date, there are no suitable clinical diagnostic, prognostic or predictive biomarkers for this neoplasia. Therefore, there is an urgent need for new MM biomarkers that enable early diagnosis and effective disease monitoring. Exosomes represent a novel source of biomarkers since they can be easily isolated from different body fluids. In this work, a primary patient-derived MM cell line enriched in CSCs was characterized by assessing the expression of specific markers and their stem-like properties. Exosomes derived from CSCs and serums from patients with MM were characterized and their metabolomic profile was analyzed by high-resolution mass spectrometry (HRMS) following an untargeted approach and applying univariate and multivariate statistical analyses. The aim of this study was to search potential biomarkers for the diagnosis of this disease. Our results showed significant metabolomic differences in exosomes derived from MM CSCs compared to those from differentiated tumour cells, and also in serumderived exosomes from patients with MM compared to those from healthy controls. Interestingly, we identified similarities between structural lipids differentially expressed in CSC-derived exosomes and those derived from patients with MM such as the glycerophosphocoline PC 16:0/0:0. To our knowledge, this is the first metabolomics-based study aimed at characterizing exosomes derived from melanoma CSCs and patients' serum in order to identify potential biomarkers for MM diagnosis. We conclude that metabolomic characterization of CSC-derived exosomes sets an open door to the discovery of clinically useful biomarkers in this neoplasia.

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Mesenchymal stem cell's secretome promotes selective enrichment of cancer stem-like cells with specific cytogenetic profile

Cited by 31 publications

References 45 publications

Cancer stem cell secretome in the tumor microenvironment: a key point for an effective personalized cancer treatment

Cancer stem cell secretome in the tumor microenvironment: a key point for an effective personalized cancer treatment

A Marine Collagen-Based Biomimetic Hydrogel Recapitulates Cancer Stem Cell Niche and Enhances Progression and Chemoresistance in Human Ovarian Cancer

Metabolomic profile of cancer stem cell‐derived exosomes from patients with malignant melanoma

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