Sunday, January 31, 2010

CSC news roundup 2010-01-31

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.

Wednesday, January 27, 2010

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.

Saturday, January 16, 2010

CSC news roundup 2010-01-16

Tuesday, January 5, 2010

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).

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.

Sunday, January 3, 2010

CSC news roundup 2010-01-03