Wednesday, June 17, 2009

Malignant Pleural Effusions (MPE) as a model

Researchers Develop Model that May Help Identify Lung Cancer Stem Cells, News Release, UCLA Jonsson Comprehensive Cancer Center, June 16, 2009. First paragraph:
Researchers at UCLA’s Jonsson Comprehensive Cancer Center, on a quest to find lung cancer stem cells, have developed a unique model to allow further investigation into the cells that many believe may be at the root of all lung cancers.
See also: Researchers Use Malignant Pleural Effusion as Model for Lung Cancer, Genetic Engineering & Biotechnology News, June 16, 2009.

Based on: The Malignant Pleural Effusion as a Model to Investigate Intratumoral Heterogeneity in Lung Cancer by Saroj K Basak and 7 co-authors, including Raj K Batra, PLoS ONE 2009(Jun 12); 4(6): e5884 [Entry in FriendFeed]. Abstract:
Malignant Pleural Effusions (MPE) may be useful as a model to study hierarchical progression of cancer and/or intratumoral heterogeneity. To strengthen the rationale for developing the MPE-model for these purposes, we set out to find evidence for the presence of cancer stem cells (CSC) in MPE and demonstrate an ability to sustain intratumoral heterogeneity in MPE-primary cultures. Our studies show that candidate lung CSC-expression signatures (PTEN, OCT4, hTERT, Bmi1, EZH2 and SUZ12) are evident in cell pellets isolated from MPE, and MPE-cytopathology also labels candidate-CSC (CD44, cMET, MDR-1, ALDH) subpopulations. Moreover, in primary cultures that use MPE as the source of both tumor cells and the tumor microenvironment (TME), candidate CSC are maintained over time. This allows us to live-sort candidate CSC-fractions from the MPE-tumor mix on the basis of surface markers (CD44, c-MET, uPAR, MDR-1) or differences in xenobiotic metabolism (ALDH). Thus, MPE-primary cultures provide an avenue to extract candidate CSC populations from individual (isogenic) MPE-tumors. This will allow us to test whether these cells can be discriminated in functional bioassays. Tumor heterogeneity in MPE-primary cultures is evidenced by variable immunolabeling, differences in colony-morphology, and differences in proliferation rates of cell subpopulations. Collectively, these data justify the ongoing development of the MPE-model for the investigation of intratumoral heterogeneity, tumor-TME interactions, and phenotypic validation of candidate lung CSC, in addition to providing direction for the pre-clinical development of rational therapeutics.

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