Review about retroviral-induced leukemogenesis and the CSC hypothesis

Hematopoietic stem cells and retroviral infection by Prabal Banerjee, Lindsey Crawford, Elizabeth Samuelson and Gerold Feuer, Retrovirology 2010(Feb 4); 7(1): 8 [Epub ahead of print][Connotea bookmark][[FriendFeed entry][PubMed Citation][Full text (PDF)].

Includes sections on Leukemia Stem Cells/Cancer Stem Cells (LSC/CSC) and on The Cancer Stem Cell Hypothesis.

CSC news roundup 2010-01-31

• Hypoxia inducible factors in CSC [FriendFeed entry] [Connotea bookmark]


• Pluripotency factors Lin28 and Oct4 identify a sub-population of stem cell-like cells in ovarian cancer [FriendFeed entry] http://is.gd/73pVk


• Evidence for self-renewing lung cancer stem cells and their implications [FriendFeed entry] [Connotea bookmark]


• The elaboration of a critical framework for understanding cancer: the CSC hypothesis [FriendFeed entry][Connotea bookmark]


• IMUC’s ICT-107 vaccine product candidate targets CSC [FriendFeed entry] http://bit.ly/5BnV5q


• Putative CSC markers show strong prognostic significance in colorectal cancer [FriendFeed entry][Connotea bookmark] http://bit.ly/7uUuOZ


• Cell of Origin Identified for Common Type of Breast Cancer [FriendFeed entry] http://bit.ly/4B0GOl http://bit.ly/5n9Icz


• Cancer Biomarker Chase Accelerates [FriendFeed entry] http://bit.ly/57iVWN


• CSC suppress immune response against brain tumor [FriendFeed entry] http://bit.ly/6HgW1g


• About a new report: Targeting CSC: Therapeutic Strategies and Pipeline Developments [FriendFeed entry] http://bit.ly/8mfqET


• More evidence that tumours, like healthy organs, grow from SC. The Economist, 14 Jan 2010 [FriendFeed entry] http://bit.ly/4AeekG


• AC133 Epitope, but not the CD133 Protein, Is Lost upon CSC differentiation [FriendFeed entry] http://bit.ly/6r2aGh


• Nanosystems capture and destroy circulating tumor cells (CTC) [FriendFeed entry] http://bit.ly/7ebzXI


• Evidence that CSC escape and down-regulate host antitumor immunity [FriendFeed entry] http://bit.ly/5vWN8n http://bit.ly/5wgRBV


• Stem cells linked to an aggressive cancer of childhood [FriendFeed entry] http://bit.ly/73ldYl http://bit.ly/6YaniV


• Role for the SCF-c-kit signaling axis in self-renewal and proliferation of human lung CSC [FriendFeed entry] http://bit.ly/6PxEyW


• High-throughput screening of tumor-initiating cells in zebrafish [FriendFeed entry] http://bit.ly/6G06No


• The Telomerase Antagonist, Imetelstat, Efficiently Targets Glioblastoma Tumor-Initiating Cells [FriendFeed entry] http://icio.us/t0td2z


• OncoMed, Fluidigm to Analyze Tumor Cell Populations [FriendFeed entry] http://bit.ly/7GnYvm


• Therapy which fails to target CSC can actually promote malignant features in the recurring tumor! [FriendFeed entry] http://bit.ly/6h7jOp


• CXCR1 blockade selectively targets human breast CSC in vitro and in xenografts [FriendFeed entry] http://bit.ly/69ynfK

Analyzing tumors as ecosystems

Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype by So Yeon Park and 4 co-authors, including Kornelia Polyak, J Clin Invest 2010(Jan 25) [Epub ahead of print][FriendFeed entry][Connotea bookmark][Full text is publicly accessible (via Gratis OA)]. PubMed Abstract:

Intratumor genetic heterogeneity is a key mechanism underlying tumor progression and therapeutic resistance. The prevailing model for explaining intratumor diversity, the clonal evolution model, has recently been challenged by proponents of the cancer stem cell hypothesis. To investigate this issue, we performed combined analyses of markers associated with cellular differentiation states and genotypic alterations in human breast carcinomas and evaluated diversity with ecological and evolutionary methods. Our analyses showed a high degree of genetic heterogeneity both within and between distinct tumor cell populations that were defined based on markers of cellular phenotypes including stem cell-like characteristics. In several tumors, stem cell-like and more-differentiated cancer cell populations were genetically distinct, leading us to question the validity of a simple differentiation hierarchy-based cancer stem cell model. The degree of diversity correlated with clinically relevant breast tumor subtypes and in some tumors was markedly different between the in situ and invasive cell populations. We also found that diversity measures were associated with clinical variables. Our findings highlight the importance of genetic diversity in intratumor heterogeneity and the value of analyzing tumors as distinct populations of cancer cells to more effectively plan treatments.

The final sentence of the Discussion section of the full text:

In summary, in this study we have demonstrated the power of analyzing tumors as ecosystems and suggest that quantitative measures of intratumor diversity might be clinically useful biomarkers predicting prognosis and response to treatment.

Another recent article from the same group: Heterogeneity for Stem Cell–Related Markers According to Tumor Subtype and Histologic Stage in Breast Cancer by So Yeon Park and 5 co-authors, including Kornelia Polyak, Clin Cancer Res 2010; 16(3): 876–87 [Epub 2010(Jan 26)][FriendFeed entry][Connotea bookmark][PubMed Citation].

From the Conclusions section of the abstract:

Our findings suggest that in breast cancer, the frequency of tumor cells positive for stem cell-like and more differentiated cell markers varies according to tumor subtype and histologic stage.

Molecular signatures of quiescent, mobilized and leukemia-initiating hematopoietic SC

Molecular Signatures of Quiescent, Mobilized and Leukemia-Initiating Hematopoietic Stem Cells by E Camilla Forsberg and 6 co-authors, including Irving L Weissman, PLoS One 2010(Jan 20);5(1):e8785. [Connotea bookmark][FriendFeed entry][Full text is publicly accessible (via Libre OA)]. PubMed Abstract:

Hematopoietic stem cells (HSC) are rare, multipotent cells capable of generating all specialized cells of the blood system. Appropriate regulation of HSC quiescence is thought to be crucial to maintain their lifelong function; however, the molecular pathways controlling stem cell quiescence remain poorly characterized. Likewise, the molecular events driving leukemogenesis remain elusive. In this study, we compare the gene expression profiles of steady-state bone marrow HSC to non-self-renewing multipotent progenitors; to HSC treated with mobilizing drugs that expand the HSC pool and induce egress from the marrow; and to leukemic HSC in a mouse model of chronic myelogenous leukemia. By intersecting the resulting lists of differentially regulated genes we identify a subset of molecules that are downregulated in all three circumstances, and thus may be particularly important for the maintenance and function of normal, quiescent HSC. These results identify potential key regulators of HSC and give insights into the clinically important processes of HSC mobilization for transplantation and leukemic development from cancer stem cells.

CSC suppress immune response against brain tumor

Cancer stem cells suppress immune response against brain tumor, News Release, The University of Texas M. D. Anderson Cancer Center, January 15, 2010.

About two publications, one in Clin Cancer Res 2010(Jan 15);16(2):461-73 and the other in Mol Cancer Ther 2010(Jan);9(1):67-78.

See also: Cancer stem cells suppress immune response against brain tumor, Science Blog, January 15, 2010, and, Mechanism that helps brain cancer evade immune system attack discovered, Science News, January 16, 2010.

CSC news roundup 2010-01-16

• Medium and Device for Proliferation of Stem Cells and Treatment of Cancer-Related Stem Cell with Resveratrol, United States Patent Application 20100010099. Via FreePatentsOnline.com. Publication Date: January 14, 2010. Assignees: Taipei Veterans General Hospital. [Patentdocs entry].


• Biological and Molecular Heterogeneity of Breast Cancers Correlates with Their Cancer Stem Cell Content by Salvatore Pece and 9 co-authors, including Pier Paolo Di Fiore, Cell 2010(Jan 8); 140(1): 62-73. [Connotea bookmark][FriendFeed entry].


• Regulating Cancer Stem Cells the miR Way by Marcus E Peter, Cell Stem Cell 2010(Jan 8); 6(1): 4-6. [Commentary on Nat Cell Biol 2009(Dec);11(12):1487-95].


• BCR-ABL enhances differentiation of long-term repopulating hematopoietic stem cells by Mirle Schemionek and 16 co-authors, including Steffen Koschmieder, Blood 2010(Jan 6) [Epub ahead of print][PubMed Citation][Connotea bookmark].


• Blocking inflammation receptor kills breast cancer stem cells, study finds, News Release, University of Michigan Health System, January 4, 2010. [About: J Clin Invest doi:10.1172/JCI39397][FriendFeed entry][Another FriendFeed entry].


• Geron Announces Publication of Data on Its Telomerase Inhibitor in Glioblastoma, Business Wire, January 4, 2010. [About: Clin Cancer Res 2010(Jan 1);16(1):154-63][FriendFeed entry].


• Primary brain tumors, neural stem cell, and brain tumor cancer cells: Where is the link? By Isabelle Germano, Victoria Swiss and Patrizia Casaccia, Neuropharmacology 2010(Jan 1) [Epub ahead of print][PubMed Citation][Connotea bookmark].


• Cancer Stem Cell Tumor Model Reveals Invasive Morphology and Increased Phenotypical Heterogeneity by Andrea Sottoriva, Joost JC Verhoeff and 6 co-authors, Cancer Res 2010(Jan 1); 70(1): 46-56. [PubMed Citation][FriendFeed entry][ResearchGATE entry].


• The therapeutic promise of the cancer stem cell concept by Natasha Y Frank, Tobias Schatton and Markus H Frank. Review in J Clin Invest 2010(Jan); 120(1): 41-50. [PubMed Citation][ResearchGATE entry].


• Prognostic impact of ALDH1 in breast cancer: a story of stem cells and tumor microenvironment, Breast Cancer Res Treat 2009(Nov 13) [Epub ahead of print][PubMed Citation][MDLinx Oncology Summary][FriendFeed entry].

US Patent 7632678 about CSC

Cancer stem cells and uses thereof, United States Patent 7632678. Issued on December 15, 2009. (Filing Date was November 22, 2006).

Inventors: Loen M Hansford, Kristen M Smith, Alessandro Datti, Freda M Miller and David R Kaplan (Toronto, Canada).

Assignee: The Hospital for Sick Children (Toronto, Ontario, Canada).

Abstract:

Disclosed are enriched preparations of neuroblastoma tumor initiating cells (NB TICs). The NB TICs are capable of self-renewal, initiating neuroblastoma tumor growth in vivo and are capable of being passaged in high frequency. These NB TICs have chromosomal abnormalities and are capable of giving rise to secondary tumor spheres. Methods are also disclosed for preparing the enriched preparations of NB TICs, such as from neuroblastoma tumor tissue and metastasized bone marrow. Also disclosed are methods of screening candidate substances to identify therapeutic agents for the treatment of neuroblastoma. Methods are also provided for screening a sample for neuroblastoma, as well as for screening a sample to identify the stage of neuroblastoma present. Kits are also provided for selecting appropriate anti-neuroblastoma compounds for a patient, and utilize isolated compositions of the patients' neuroblastoma tumor initiating cells. In this manner, a customized medicinal profile for the patient may be devised.