Do Cancer Stem Cells have an Immunomodulatory Role Different from the Bulk of Tumor Cells?

Ghebeh, Hazem; Al‐Alwan, Monther

doi:10.4172/2157-2518.s14-003

Cited by 10 publications

(11 citation statements)

References 65 publications

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“…We previously showed that IGF-1 facilitated immune escape by decreasing the immunogenicity of the murine melanoma B16-F0 cell line [26]. Furthermore, the immunomodulatory properties of tumor cells have recently been linked to EMT and stemness, consistent with a role for CICs in immune escape [15, 58–59]. Indeed, ABCB5 + MICs have been shown to induce immune responses less efficiently than the ABCB5 − bulk of the tumor [59].…”

Section: Discussionmentioning

confidence: 99%

IGF-1 contributes to the expansion of melanoma-initiating cells through an epithelial-mesenchymal transition process

et al. 2016

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Melanoma is a particularly virulent human cancer, due to its resistance to conventional treatments and high frequency of metastasis. Melanomas contain a fraction of cells, the melanoma-initiating cells (MICs), responsible for tumor propagation and relapse. Identification of the molecular pathways supporting MICs is, therefore, vital for the development of targeted treatments. One factor produced by melanoma cells and their microenvironment, insulin-like growth factor-1 (IGF- 1), is linked to epithelial-mesenchymal transition (EMT) and stemness features in several cancers.We evaluated the effect of IGF-1 on the phenotype and chemoresistance of B16-F10 cells. IGF-1 inhibition in these cells prevented malignant cell proliferation, migration and invasion, and lung colony formation in immunodeficient mice. IGF-1 downregulation also markedly inhibited EMT, with low levels of ZEB1 and mesenchymal markers (N-cadherin, CD44, CD29, CD105) associated with high levels of E-cadherin and MITF, the major regulator of melanocyte differentiation. IGF-1 inhibition greatly reduced stemness features, including the expression of key stem markers (SOX2, Oct-3/4, CD24 and CD133), and the functional characteristics of MICs (melanosphere formation, aldehyde dehydrogenase activity, side population). These features were associated with a high degree of sensitivity to mitoxantrone treatment.In this study, we deciphered new connections between IGF-1 and stemness features and identified IGF-1 as instrumental for maintaining the MIC phenotype. The IGF1/IGF1-R nexus could be targeted for the development of more efficient anti-melanoma treatments. Blocking the IGF-1 pathway would improve the immune response, decrease the metastatic potential of tumor cells and sensitize melanoma cells to conventional treatments.

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Section: Discussionmentioning

confidence: 99%

IGF-1 contributes to the expansion of melanoma-initiating cells through an epithelial-mesenchymal transition process

et al. 2016

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“…These cancer stem cells, owing to their slow replication, are intrinsically resistant to radiotherapy and are only partially sensitive to chemotherapy [44, 45]. Additionally, the stem cell sub-populations have a strong immune-suppressive effect on the tumor microenvironment [46]. This phenomenon has been captured in our model in the study of the temporal evolution of the tumor-immune interaction dynamics, where we observe that coincident with the proliferation of the stem and resistant stem cell there is also an increased proliferation of the M2 and Treg cells (Fig 2C).…”

Section: Discussionmentioning

confidence: 99%

Exploring immuno-regulatory mechanisms in the tumor microenvironment: Model and design of protocols for cancer remission

Ganguli

Sarkar

2018

PLoS ONE

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The tumor microenvironment comprising of the immune cells and cytokines acts as the ‘soil’ that nourishes a developing tumor. Lack of a comprehensive study of the interactions of this tumor microenvironment with the heterogeneous sub-population of tumor cells that arise from the differentiation of Cancer Stem Cells (CSC), i.e. the ‘seed’, has limited our understanding of the development of drug resistance and treatment failures in Cancer. Based on this seed and soil hypothesis, for the very first time, we have captured the concept of CSC differentiation and tumor-immune interaction into a generic model that has been validated with known experimental data. Using this model we report that as the CSC differentiation shifts from symmetric to asymmetric pattern, resistant cancer cells start accumulating in the tumor that makes it refractory to therapeutic interventions. Model analyses unveiled the presence of feedback loops that establish the dual role of M2 macrophages in regulating tumor proliferation. The study further revealed oscillations in the tumor sub-populations in the presence of TH1 derived IFN-γ that eliminates CSC; and the role of IL10 feedback in the regulation of TH1/TH2 ratio. These analyses expose important observations that are indicative of Cancer prognosis. Further, the model has been used for testing known treatment protocols to explore the reasons of failure of conventional treatment strategies and propose an improvised protocol that shows promising results in suppressing the proliferation of all the cellular sub-populations of the tumor and restoring a healthy TH1/TH2 ratio that assures better Cancer remission.

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“…Immune inhibitory molecules like B7-H1 is expressed on tumor cells (tumor infiltrating lymphocytes) and FOXP3+ regulatory T-cells are abundant in the tumor microenvironment in a group of breast cancer patients. Besides, CSCs produce immunosuppressive molecules such as TGF-β, PG E2 and adenosine, or of cytokines such as IL-6 and IL-10, the resistance to apoptosis, and/or the expression of Fas ligand (FasL), which leads to the death of tumor-infiltrating lymphocytes [73]. CSCs would be largely unaffected by standard therapies, because of their stem cell characteristics.…”

Section: Cancer Stem Cells Role In Cancermentioning

confidence: 99%

Stem Cells and Cancer

Ali¹

2016

J Cell Sci Ther

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Stem cells are undifferentiated cells that can differentiate into specialized cell and can divide to produce more stem cells. The concept of cancer stem cells has been discussed in the scientific literature since the 19th century. Circumstantial evidence suggests that most tumors are heterogeneous and contain a small population of cancer stem cells that exhibit distinctive self-renewal, proliferation and differentiation capabilities, which are believed to play a crucial role in tumor progression, drug resistance, recurrence and metastasis in multiple malignancies. Unlike normal adult stem cells that remain constant in number, cancer stem cells can increase in number as tumors grow, and give rise to progeny that can be both locally invasive and colonize distant sites-the two hallmarks of malignancy. Rapid advances in the cancer stem cell field have provided cause for optimism for the development of more reliable cancer therapies in the future. Strategies aimed at efficient targeting of cancer stem cells are becoming important for monitoring the progress of cancer therapy and for evaluating new therapeutic approaches.

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Do Cancer Stem Cells have an Immunomodulatory Role Different from the Bulk of Tumor Cells?

Cited by 10 publications

References 65 publications

IGF-1 contributes to the expansion of melanoma-initiating cells through an epithelial-mesenchymal transition process

IGF-1 contributes to the expansion of melanoma-initiating cells through an epithelial-mesenchymal transition process

Exploring immuno-regulatory mechanisms in the tumor microenvironment: Model and design of protocols for cancer remission

Stem Cells and Cancer

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