Reprogramming of cancer stem cells into non-tumorigenic cells using stem cell exosomes for cancer therapy

The cancer stem cell model proposes that tumors have a hierarchical organization in which tumorigenic cells give rise to non-tumorigenic cells, with only a subset of stem-like cells able to propagate the tumor. In the case of prostate cancer, recent analyses of genetically engineered mouse (GEM) models have provided evidence supporting the existence of cancer stem cells in vivo. These studies suggest that cancer stem cells capable of tumor propagation exist at various stages of tumor progression from prostatic intraepithelial neoplasia (PIN) to advanced metastatic and castration-resistant disease. However, studies of stem cells in prostate cancer have been limited by available approaches for evaluating their functional properties in cell culture and transplantation assays. Given the role of the tumor microenvironment and the putative cancer stem cell niche, future studies using GEM models to analyze cancer stem cells in their native tissue microenvironment are likely to be highly informative.

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Faculty Opinions recommendation of The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.10883956.12086056 ◽

2011 ◽

Author(s):

Kim Jensen ◽

Robert Fordham

Keyword(s):

Colorectal Cancer ◽

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cells ◽

Intestinal Stem Cell ◽

Disease Relapse ◽

Colorectal Cancer Stem Cells

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Integrin α6 (CD49f), The Microenvironment and Cancer Stem Cells

Current Stem Cell Research & Therapy ◽

10.2174/1574888x13666181002151330 ◽

2019 ◽

Vol 14 (5) ◽

pp. 428-436 ◽

Cited By ~ 4

Author(s):

Gabriele D. Bigoni-Ordóñez ◽

Daniel Czarnowski ◽

Tyler Parsons ◽

Gerard J. Madlambayan ◽

Luis G. Villa-Diaz

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cells ◽

Cancer Stem Cell ◽

The Self ◽

Self Renewal ◽

Terminal Disease

Cancer is a highly prevalent and potentially terminal disease that affects millions of individuals worldwide. Here, we review the literature exploring the intricacies of stem cells bearing tumorigenic characteristics and collect evidence demonstrating the importance of integrin α6 (ITGA6, also known as CD49f) in cancer stem cell (CSC) activity. ITGA6 is commonly used to identify CSC populations in various tissues and plays an important role sustaining the self-renewal of CSCs by interconnecting them with the tumorigenic microenvironment.

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Cancer stemness as a target for immunotherapy is shaped by pro-inflammatory stress.

Current Stem Cell Research & Therapy ◽

10.2174/1574888x15666200309145901 ◽

2020 ◽

Vol 15 ◽

Author(s):

Nese Unver

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cells ◽

Immune Cells ◽

Tumor Recurrence ◽

Inflammatory Factors ◽

Cancer Stemness ◽

Self Renewal ◽

Inflammatory Stress ◽

Factors Affecting

: Cancer stem cells represent a rare subpopulation of cancer cells carrying self-renewal and differentiation features in the multi-step tumorigenesis, tumor recurrence and metastasis. Pro-inflammatory stress is highly associated with cancer stemness via induction of cytokines, tumor-promoting immune cells and cancer stemness-related signaling pathways. This review summarizes the major pro-inflammatory factors affecting cancer stem cell characteristics and the critical immunotherapeutic strategies to eliminate cancer stem cells.

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PIK3C3 Inhibition Promotes Sensitivity to Colon Cancer Therapy by Inhibiting Cancer Stem Cells

Cancers ◽

10.3390/cancers13092168 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2168

Author(s):

Balawant Kumar ◽

Rizwan Ahmad ◽

Swagat Sharma ◽

Saiprasad Gowrikumar ◽

Mark Primeaux ◽

...

Keyword(s):

Stem Cells ◽

Colon Cancer ◽

Cancer Therapy ◽

Cancer Stem Cells ◽

Side Population ◽

Therapy Resistance ◽

Fluorescent Reporter ◽

Combination Treatments ◽

Gsk 3Β ◽

Resistance To Chemotherapy

Background: Despite recent advances in therapies, resistance to chemotherapy remains a critical problem in the clinical management of colorectal cancer (CRC). Cancer stem cells (CSCs) play a central role in therapy resistance. Thus, elimination of CSCs is crucial for effective CRC therapy; however, such strategies are limited. Autophagy promotes resistance to cancer therapy; however, whether autophagy protects CSCs to promote resistance to CRC-therapy is not well understood. Moreover, specific and potent autophagy inhibitors are warranted as clinical trials with hydroxychloroquine have not been successful. Methods: Colon cancer cells and tumoroids were used. Fluorescent reporter-based analysis of autophagy flux, spheroid and side population (SP) culture, and qPCR were done. We synthesized 36-077, a potent inhibitor of PIK3C3/VPS34 kinase, to inhibit autophagy. Combination treatments were done using 5-fluorouracil (5-FU) and 36-077. Results: The 5-FU treatment induced autophagy only in a subset of the treated colon cancer. These autophagy-enriched cells also showed increased expression of CSC markers. Co-treatment with 36-077 significantly improved efficacy of the 5-FU treatment. Mechanistic studies revealed that combination therapy inhibited GSK-3β/Wnt/β-catenin signaling to inhibit CSC population. Conclusion: Autophagy promotes resistance to CRC-therapy by specifically promoting GSK-3β/Wnt/β-catenin signaling to promote CSC survival, and 36-077, a PIK3C3/VPS34 inhibitor, helps promote efficacy of CRC therapy.

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The CXCL12 Crossroads in Cancer Stem Cells and Their Niche

Cancers ◽

10.3390/cancers13030469 ◽

2021 ◽

Vol 13 (3) ◽

pp. 469

Author(s):

Juan Carlos López-Gil ◽

Laura Martin-Hijano ◽

Patrick C. Hermann ◽

Bruno Sainz

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Tumor Microenvironment ◽

Cancer Stem Cells ◽

Crucial Role ◽

Diverse Group ◽

Hematopoietic Stem ◽

Stem Cell Support ◽

Cell Support ◽

Tumor Entities

Cancer stem cells (CSCs) are defined as a subpopulation of “stem”-like cells within the tumor with unique characteristics that allow them to maintain tumor growth, escape standard anti-tumor therapies and drive subsequent repopulation of the tumor. This is the result of their intrinsic “stem”-like features and the strong driving influence of the CSC niche, a subcompartment within the tumor microenvironment that includes a diverse group of cells focused on maintaining and supporting the CSC. CXCL12 is a chemokine that plays a crucial role in hematopoietic stem cell support and has been extensively reported to be involved in several cancer-related processes. In this review, we will provide the latest evidence about the interactions between CSC niche-derived CXCL12 and its receptors—CXCR4 and CXCR7—present on CSC populations across different tumor entities. The interactions facilitated by CXCL12/CXCR4/CXCR7 axes seem to be strongly linked to CSC “stem”-like features, tumor progression, and metastasis promotion. Altogether, this suggests a role for CXCL12 and its receptors in the maintenance of CSCs and the components of their niche. Moreover, we will also provide an update of the therapeutic options being currently tested to disrupt the CXCL12 axes in order to target, directly or indirectly, the CSC subpopulation.

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Modeling the Treatment of Glioblastoma Multiforme and Cancer Stem Cells with Ordinary Differential Equations

Computational and Mathematical Methods in Medicine ◽

10.1155/2016/1239861 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 4

Author(s):

Kristen Abernathy ◽

Jeremy Burke

Keyword(s):

Stem Cells ◽

Glioblastoma Multiforme ◽

Cancer Therapy ◽

Cancer Stem Cells ◽

Differential Equations ◽

Ordinary Differential Equations ◽

Cancer Patients ◽

Tumor Cells ◽

Tumor Recurrence ◽

Common Event

Despite improvements in cancer therapy and treatments, tumor recurrence is a common event in cancer patients. One explanation of recurrence is that cancer therapy focuses on treatment of tumor cells and does not eradicate cancer stem cells (CSCs). CSCs are postulated to behave similar to normal stem cells in that their role is to maintain homeostasis. That is, when the population of tumor cells is reduced or depleted by treatment, CSCs will repopulate the tumor, causing recurrence. In this paper, we study the application of the CSC Hypothesis to the treatment of glioblastoma multiforme by immunotherapy. We extend the work of Kogan et al. (2008) to incorporate the dynamics of CSCs, prove the existence of a recurrence state, and provide an analysis of possible cancerous states and their dependence on treatment levels.

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