P44 TUMORIGENIC POTENTIAL OF CANCER STEM CELLS (CSCS) ISOLATED FROM HUMAN CHOLANGIOCARCINOMA (CCA) SUBTYPES

: 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.

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Current Strategies for Identification of Glioma Stem Cells: Adequate or Unsatisfactory?

Journal of Oncology ◽

10.1155/2012/376894 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 44

Author(s):

Paola Brescia ◽

Cristina Richichi ◽

Giuliana Pelicci

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cells ◽

Large Scale ◽

Molecular Mechanisms ◽

Cell Phenotype ◽

Multiple Tumor ◽

Early Results ◽

Tumorigenic Potential ◽

Tumor Types

Cancer stem cells (CSCs) were isolated in multiple tumor types, including human glioblastomas, and although the presence of surface markers selectively expressed on CSCs can be used to isolate them, no marker/pattern of markers are sufficiently robust to definitively identify stem cells in tumors. Several markers were evaluated for their prognostic value with promising early results, however none of them was proven to be clinically useful in large-scale studies, leading to outstanding efforts to identify new markers. Given the heterogeneity of human glioblastomas further investigations are necessary to identify both cancer stem cell-specific markers and the molecular mechanisms sustaining the tumorigenic potential of these cells to develop tailored treatments. Markers for glioblastoma stem cells such as CD133, CD15, integrin-α6, L1CAM might be informative to identify these cells but cannot be conclusively linked to a stem cell phenotype. Overlap of expression, functional state and morphology of different subpopulations lead to carefully consider the techniques employed so far to isolate these cells. Due to a dearth of methods and markers reliably identifying the candidate cancer stem cells, the isolation/enrichment of cancer stem cells to be therapeutically targeted remains a major challenge.

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Endothelial Interleukin-6 Defines the Tumorigenic Potential of Primary Human Cancer Stem Cells

Stem Cells ◽

10.1002/stem.1793 ◽

2014 ◽

Vol 32 (11) ◽

pp. 2845-2857 ◽

Cited By ~ 52

Author(s):

Sudha Krishnamurthy ◽

Kristy A. Warner ◽

Zhihong Dong ◽

Atsushi Imai ◽

Carolina Nör ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Interleukin 6 ◽

Human Cancer ◽

Tumorigenic Potential

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Exploiting oxidative phosphorylation to promote the stem and immunoevasive properties of pancreatic cancer stem cells

Nature Communications ◽

10.1038/s41467-020-18954-z ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Sandra Valle ◽

Sonia Alcalá ◽

Laura Martin-Hijano ◽

Pablo Cabezas-Sáinz ◽

Diego Navarro ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Ductal Adenocarcinoma ◽

In Vitro System ◽

Tumorigenic Potential ◽

Term Enrichment ◽

Pluripotency Gene ◽

Pancreatic Cancer Stem Cells

Abstract Pancreatic ductal adenocarcinoma (PDAC), the fourth leading cause of cancer death, has a 5-year survival rate of approximately 7–9%. The ineffectiveness of anti-PDAC therapies is believed to be due to the existence of a subpopulation of tumor cells known as cancer stem cells (CSCs), which are functionally plastic, and have exclusive tumorigenic, chemoresistant and metastatic capacities. Herein, we describe a 2D in vitro system for long-term enrichment of pancreatic CSCs that is amenable to biological and CSC-specific studies. By changing the carbon source from glucose to galactose in vitro, we force PDAC cells to utilize OXPHOS, resulting in enrichment of CSCs defined by increased CSC biomarker and pluripotency gene expression, greater tumorigenic potential, induced but reversible quiescence, increased OXPHOS activity, enhanced invasiveness, and upregulated immune evasion properties. This CSC enrichment method can facilitate the discovery of new CSC-specific hallmarks for future development into targets for PDAC-based therapies.

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KDM3 epigenetically controls tumorigenic potentials of human colorectal cancer stem cells through Wnt/β-catenin signalling

Nature Communications ◽

10.1038/ncomms15146 ◽

2017 ◽

Vol 8 (1) ◽

Cited By ~ 42

Author(s):

Jiong Li ◽

Bo Yu ◽

Peng Deng ◽

Yingduan Cheng ◽

Yongxin Yu ◽

...

Keyword(s):

Colorectal Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Gene Transcription ◽

Target Gene ◽

Histone Demethylases ◽

Human Colorectal Cancer ◽

Tumorigenic Potential ◽

Colorectal Cancer Stem Cells ◽

Target Gene Transcription

Abstract Human colorectal cancer stem cells (CSCs) are tumour initiating cells that can self-renew and are highly tumorigenic and chemoresistant. While genetic mutations associated with human colorectal cancer development are well-known, little is known about how and whether epigenetic factors specifically contribute to the functional properties of human colorectal CSCs. Here we report that the KDM3 family of histone demethylases plays an important role in tumorigenic potential and survival of human colorectal CSCs by epigenetically activating Wnt target gene transcription. The depletion of KDM3 inhibits tumorigenic growth and chemoresistance of human colorectal CSCs. Mechanistically, KDM3 not only directly erases repressive H3K9me2 marks, but also helps to recruit histone methyltransferase MLL1 to promote H3K4 methylation, thereby promoting Wnt target gene transcription. Our results suggest that KDM3 is a critical epigenetic factor in Wnt signalling that orchestrates chromatin changes and transcription in human colorectal CSCs, identifying potential therapeutic targets for effective elimination of CSCs.

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Abstract 2807: Oral silibinin inhibits tumorigenic potential of colon cancer stem cells

10.1158/1538-7445.am2015-2807 ◽

2015 ◽

Author(s):

Sushil Kumar ◽

Dileep Kumar ◽

Komal Raina ◽

Natalie J. Serkova ◽

Chapla Agarwal ◽

...

Keyword(s):

Stem Cells ◽

Colon Cancer ◽

Cancer Stem Cells ◽

Colon Cancer Stem Cells ◽

Tumorigenic Potential

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P0239 : Tumorigenic potential of Cancer Stem Cells (CSCs) isolated from human cholangiocarcinoma (CCA) subtypes in cirrhotic microenvironment

Journal of Hepatology ◽

10.1016/s0168-8278(15)30456-6 ◽

2015 ◽

Vol 62 ◽

pp. S396

Author(s):

V. Cardinale ◽

A. Renzi ◽

G. Carpino ◽

M.C. Bragazzi ◽

A. Torrice ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Tumorigenic Potential

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Role of Cancer Stem Cells in Spine Tumors

Neurosurgery ◽

10.1227/neu.0b013e3182532e71 ◽

2012 ◽

Vol 71 (1) ◽

pp. 117-125 ◽

Cited By ~ 7

Author(s):

Wesley Hsu ◽

Ahmed Mohyeldin ◽

Sagar R. Shah ◽

Ziya L. Gokaslan ◽

Alfredo Quinones-Hinojosa

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Tumor Cells ◽

Tumor Recurrence ◽

Surgical Intervention ◽

Spinal Column ◽

Primary Tumors ◽

Tumorigenic Potential ◽

Active Investigation

Abstract The management of spinal column tumors continues to be a challenge for clinicians. The mechanisms of tumor recurrence after surgical intervention as well as resistance to radiation and chemotherapy continue to be elucidated. Furthermore, the pathophysiology of metastatic spread remains an area of active investigation. There is a growing body of evidence pointing to the existence of a subset of tumor cells with high tumorigenic potential in many spine cancers that exhibit characteristics similar to those of stem cells. The ability to self-renew and differentiate into multiple lineages is the hallmark of stem cells, and tumor cells that exhibit these characteristics have been described as cancer stem cells (CSCs). The mechanisms that allow nonmalignant stem cells to promote normal developmental programming by way of enhanced proliferation, promotion of angiogenesis, and increased motility may be used by CSCs to fuel carcinogenesis. The purpose of this review is to discuss what is known about the role of CSCs in tumors of the osseous spine. First, this article reviews the fundamental concepts critical to understanding the role of CSCs with respect to chemoresistance, radioresistance, and metastatic disease. This discussion is followed by a review of what is known about the role of CSCs in the most common primary tumors of the osseous spine.

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Tumorigenic potential of cancer stem cells (CSCs) isolated from human cholangiocarcinoma (CCA) subtypes

Digestive and Liver Disease ◽

10.1016/j.dld.2014.01.126 ◽

2014 ◽

Vol 46 ◽

pp. e57

Author(s):

A. Torrice ◽

G. Carpino ◽

A. Fraveto ◽

A. Renzi ◽

M.C. Bragazzi ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Tumorigenic Potential

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Drug-eluting microarrays to identify effective chemotherapeutic combinations targeting patient-derived cancer stem cells

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1505374112 ◽

2015 ◽

Vol 112 (28) ◽

pp. 8732-8737 ◽

Cited By ~ 16

Author(s):

Matthew R. Carstens ◽

Robert C. Fisher ◽

Abhinav P. Acharya ◽

Elizabeth A. Butterworth ◽

Edward Scott ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Solid Substrate ◽

New Paradigm ◽

Drug Candidates ◽

Treatment Conditions ◽

Tumorigenic Potential ◽

Drug Eluting ◽

Minimal Quantity ◽

Rare Cells

A new paradigm in oncology establishes a spectrum of tumorigenic potential across the heterogeneous phenotypes within a tumor. The cancer stem cell hypothesis postulates that a minute fraction of cells within a tumor, termed cancer stem cells (CSCs), have a tumor-initiating capacity that propels tumor growth. An application of this discovery is to target this critical cell population using chemotherapy; however, the process of isolating these cells is arduous, and the rarity of CSCs makes it difficult to test potential drug candidates in a robust fashion, particularly for individual patients. To address the challenge of screening drug libraries on patient-derived populations of rare cells, such as CSCs, we have developed a drug-eluting microarray, a miniaturized platform onto which a minimal quantity of cells can adhere and be exposed to unique treatment conditions. Hundreds of drug-loaded polymer islands acting as drug depots colocalized with adherent cells are surrounded by a nonfouling background, creating isolated culture environments on a solid substrate. Significant results can be obtained by testing <6% of the cells required for a typical 96-well plate. Reliability was demonstrated by an average coefficient of variation of 14% between all of the microarrays and 13% between identical conditions within a single microarray. Using the drug-eluting array, colorectal CSCs isolated from two patients exhibited unique responses to drug combinations when cultured on the drug-eluting microarray, highlighting the potential as a prognostic tool to identify personalized chemotherapeutic regimens targeting CSCs.

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