Revisiting the dynamic cancer stem cell model: Importance of tumour edges

Hernández-Camarero, Pablo; Jiménez, Gema; López‐Ruiz, Elena; Barungi, Shivan; Marchal, Juan A.; Perán, Macarena

doi:10.1016/j.critrevonc.2018.08.004

Cited by 31 publications

(32 citation statements)

References 115 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Successful metastasis requires a favorable environment for the colonization and growth of tumor cells at the site of the secondary tumor, called the premetastatic niche (PMN) [187]. This PMN requires the recruitment and activation of local resident cells, alteration of the existing vasculature, ECM remodeling, as well as immune system deregulation [187,188]. Several factors secreted by CSCs are involved in PMN formation.…”

Section: Secretome In Metastasismentioning

confidence: 99%

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

et al. 2020

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Secretome In Metastasismentioning

confidence: 99%

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

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…The action of the secretome, which includes extracellular vesicles, cytokines, miRNAs, or mRNAs released by the cells in the surrounding tissue, promotes the conversion of the phenotype of the differentiated tumor cells in the tumor edges into undifferentiated CSCs. These CSCs can invade adjacent areas and enter the vascular and lymphatic systems facilitating distant spread [ 39 ].…”

Section: Csc Subpopulationmentioning

confidence: 99%

“…TME is not only essential for the shape, function, development, and growth of tissues [ 96 , 100 , 107 ], but also for maintaining the optimal conditions of CSCs [ 39 , 61 , 96 , 108 ] and promoting tumor growth [ 109 ]. Within the TME, CSCs reside in specific areas known as CSC niches, where they can survive, self-renew, reactivate [ 30 , 61 , 75 , 110 ], and maintain their plasticity due to the autocrine and paracrine signals provided by the TME [ 111 , 112 , 113 ].…”

Section: Cscs and Microenvironmentmentioning

confidence: 99%

CSC Radioresistance: A Therapeutic Challenge to Improve Radiotherapy Effectiveness in Cancer

Olivares-Urbano

Griñán‐Lisón

Marchal

et al. 2020

Cells

Self Cite

135

View full text Add to dashboard Cite

Radiotherapy (RT) is a modality of oncologic treatment that can be used to treat approximately 50% of all cancer patients either alone or in combination with other treatment modalities such as surgery, chemotherapy, immunotherapy, and therapeutic targeting. Despite the technological advances in RT, which allow a more precise delivery of radiation while progressively minimizing the impact on normal tissues, issues like radioresistance and tumor recurrence remain important challenges. Tumor heterogeneity is responsible for the variation in the radiation response of the different tumor subpopulations. A main factor related to radioresistance is the presence of cancer stem cells (CSC) inside tumors, which are responsible for metastases, relapses, RT failure, and a poor prognosis in cancer patients. The plasticity of CSCs, a process highly dependent on the epithelial–mesenchymal transition (EMT) and associated to cell dedifferentiation, complicates the identification and eradication of CSCs and it might be involved in disease relapse and progression after irradiation. The tumor microenvironment and the interactions of CSCs with their niches also play an important role in the response to RT. This review provides a deep insight into the characteristics and radioresistance mechanisms of CSCs and into the role of CSCs and tumor microenvironment in both the primary tumor and metastasis in response to radiation, and the radiobiological principles related to the CSC response to RT. Finally, we summarize the major advances and clinical trials on the development of CSC-based therapies combined with RT to overcome radioresistance. A better understanding of the potential therapeutic targets for CSC radiosensitization will provide safer and more efficient combination strategies, which in turn will improve the live expectancy and curability of cancer patients.

show abstract

“…This suggests that 4 Gy selected the more resistant triple‐negative BCSCs in vitro , which had more aggressive behavior in vivo . In fact, the great heterogeneity of BCSC (Da Cruz Paula and Lopes, ; Hernández‐Camarero et al , ) has been reported and that CSC plasticity may be a common response to IR with the generation of new induced BCSCs resistant to specific IR doses, specifically SUM159PT ALDH‐ triple‐negative BCSCs tumors irradiated with 4Gy, induced more aggressive BCSC subpopulations (Lagadec et al , ). In addition, high levels of VIMENTIN, an indicator of BC progression (Calaf et al , ), were found in tumors derived from monolayer cultures irradiated with 2 Gy, and those derived by mammospheres irradiated with 4 Gy showing concordance with EMT‐gene expression found in vitro .…”

Section: Discussionmentioning

confidence: 99%

miRNAs as radio‐response biomarkers for breast cancer stem cells

et al. 2020

Self Cite

View full text Add to dashboard Cite

In breast cancer (BC), the presence of cancer stem cells (CSCs) has been related to relapse, metastasis, and radioresistance. Radiotherapy (RT) is an extended BC treatment, but is not always effective. CSCs have several mechanisms of radioresistance in place, and some miRNAs are involved in the cellular response to ionizing radiation (IR). Here, we studied how IR affects the expression of miRNAs related to stemness in different molecular BC subtypes. Exposition of BC cells to radiation doses of 2, 4, or 6 Gy affected their phenotype, functional characteristics, pluripotency gene expression, and in vivo tumorigenic capacity. This held true for various molecular subtypes of BC cells (classified by ER, PR and HER‐2 status), and for BC cells either plated in monolayer, or being in suspension as mammospheres. However, the effect of IR on the expression of eight stemness‐ and radioresistance‐related miRNAs (miR‐210, miR‐10b, miR‐182, miR‐142, miR‐221, miR‐21, miR‐93, miR‐15b) varied, depending on cell line subpopulation and clinicopathological features of BC patients. Therefore, clinicopathological features and, potentially also, chemotherapy regimen should be both taken into consideration, for determining a potential miRNA signature by liquid biopsy in BC patients treated with RT. Personalized and precision RT dosage regimes could improve the prognosis, treatment, and survival of BC patients.

show abstract

Revisiting the dynamic cancer stem cell model: Importance of tumour edges

Cited by 31 publications

References 115 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

CSC Radioresistance: A Therapeutic Challenge to Improve Radiotherapy Effectiveness in Cancer

miRNAs as radio‐response biomarkers for breast cancer stem cells

Contact Info

Product

Resources

About