Fighting Cancer Stem Cells Via Armored Mesenchymal Stem Cells with Napabucasin: A New Strategy for Cancer Therapy

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.

Download Full-text

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.

Download Full-text

Targeting pancreatic cancer stem cells for cancer therapy

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer ◽

10.1016/j.bbcan.2012.06.002 ◽

2012 ◽

Vol 1826 (2) ◽

pp. 385-399 ◽

Cited By ~ 6

Author(s):

Jun Xia ◽

Changjie Chen ◽

Zhiwen Chen ◽

Lucio Miele ◽

Fazlul H. Sarkar ◽

...

Keyword(s):

Pancreatic Cancer ◽

Stem Cells ◽

Cancer Therapy ◽

Cancer Stem Cells ◽

Pancreatic Cancer Stem Cells

Download Full-text

Detonation nanodiamond complexes with cancer stem cells inhibitors or paracrine products of mesenchymal stem cells as new potential medications

Crystallography Reports ◽

10.1134/s1063774515050041 ◽

2015 ◽

Vol 60 (5) ◽

pp. 763-767 ◽

Cited By ~ 3

Author(s):

A. G. Konoplyannikov ◽

A. E. Alekseenskiy ◽

S. G. Zlotin ◽

B. B. Smirnov ◽

S. Sh. Kalsina ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cancer Stem Cells ◽

Detonation Nanodiamond

Download Full-text

Bone Marrow Mesenchymal Stem Cells (BMSCs) Restrain the Malignant Behaviors of A549 Lung Cancer Cells Under Hypoxia via miR-145

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2022.2926 ◽

2022 ◽

Vol 12 (3) ◽

pp. 597-601

Author(s):

Haibin Song ◽

Heng Zhang ◽

Lei Li

Keyword(s):

Lung Cancer ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Cancer Stem Cells ◽

Cell Invasion ◽

A549 Cells ◽

Hypoxia Group ◽

Marrow Mesenchymal Stem Cells ◽

Lung Cancer Stem Cells

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.

Download Full-text

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.

Download Full-text