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Discrimination between circulating endothelial cells and blood cell populations with overlapping phenotype reveals distinct regulation and predictive potential in cancer therapy.

ABSTRACT: BACKGROUND:Circulating endothelial cells (CECs) have been proposed to predict patient response to antiangiogenic cancer therapy. However, contradictory reports and inconsistency in the phenotypic identification of CECs have led us to compare three cell populations with partially overlapping phenotype in cancer patients receiving chemotherapy and the antiangiogenic agent bevacizumab. METHODS:Patients (n = 20) with locally advanced pancreatic cancer were monitored during 16 weeks of neoadjuvant treatment with gemcitabine and bevacizumab. Detection of circulating cell populations was based on the marker combination CD45, CD31, and CD146; levels of viable and dead (7-aminoactinomycin D-positive) cells were evaluated by flow cytometry in 2-week intervals. RESULTS:We were able to discriminate and concomitantly monitor three cell populations elevated in cancer patients. Whereas CECs were defined as CD45(-) CD31(+) CD146(+), the distinct populations of CD45(-) CD31(-) CD146(+) and CD45(-) CD31(high) CD146(-) cells were partly positive for CD3 and CD41, respectively. CECs and CD45(-) CD31(-) CD146(+) cells increased during therapy; the rise in dead cells was positively correlated with patient response or survival. Conversely, CD45(-) CD31(high) CD146(-) cells decreased in neoadjuvant treatment. A highly significant correlation was established for improved patient response and a minor decrease in viable cell counts. CONCLUSIONS:Flow cytometric CEC analysis based on CD45, CD31, and CD146 requires careful discrimination between blood cell populations with overlapping phenotype showing hallmarks of activated T cells and large platelets. However, these three cell populations show distinct regulation during cancer therapy, and their concomitant analysis may offer extended prognostic and predictive information.

SUBMITTER: Starlinger P

PROVIDER: S-EPMC3201574 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Discrimination between circulating endothelial cells and blood cell populations with overlapping phenotype reveals distinct regulation and predictive potential in cancer therapy.

Starlinger Patrick P Brugger Philipp P Reiter Christian C Schauer Dominic D Sommerfeldt Silvia S Tamandl Dietmar D Kuehrer Irene I Schoppmann Sebastian F SF Gnant Michael M Brostjan Christine C

Neoplasia (New York, N.Y.) 20111001 10

<h4>Background</h4>Circulating endothelial cells (CECs) have been proposed to predict patient response to antiangiogenic cancer therapy. However, contradictory reports and inconsistency in the phenotypic identification of CECs have led us to compare three cell populations with partially overlapping phenotype in cancer patients receiving chemotherapy and the antiangiogenic agent bevacizumab.<h4>Methods</h4>Patients (n = 20) with locally advanced pancreatic cancer were monitored during 16 weeks of ...[more]

PMID: 22028623

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Project description:The chronological lifespan (CLS) of Saccharomyces cerevisiae is defined as the number days that non-dividing cells remain viable, typically in stationary phase cultures or in water. CLS is extended by restricting glucose in the starting cultures, and is considered a form of caloric restriction (CR). Through a previous genetic screen our lab determined that deleting components of the de novo purine biosynthesis pathway also significantly increased CLS. Significant similarities in gene expression profiles between calorie restricted WT cells and a non-restricted ade4M-bM-^HM-^F mutant suggested the possibility of common gene expression biomarkers of all chronologically long lived cells that could also provide insights into general mechanisms of lifespan extension. We have identified additional growth conditions that extend CLS of WT cells, including supplementation of the media with isonicotinamide (INAM), a known sirtuin activator, or by supplementation with a concentrate collected from the expired media of a calorie restricted yeast culture, presumably due to an as yet unidentified longevity factor. Using these varied methods to extend CLS, we compared gene expression profiles in the aging cells (at day 8) to identify functionally relevant biomarkers of longevity. Nineteen genes were differentially regulated in all 4 of the long-lived populations relative to wild type. Of these 19 genes, viable haploid deletion mutants were available for 16 of them, and 12 were found to have a significant impact on CLS. Duplicate cultures were grown to saturation in SC media cultures, aged, and then harvested on day 8. The deletion mutant ade4M-bM-^HM-^F as well as WT cells treated with 25 mM isonicotinamide, calorie restricted (0.5% glucose), or treated with expired media concentrate from previously calorie restricted cultures. These 4 conditions were then compared to a wild-type (WT) strain. Total RNA was isolated and used for microarray hybridizations onto Affymetrix Yeast 2.0 Gene arrrays.

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Discrimination between circulating endothelial cells and blood cell populations with overlapping phenotype reveals distinct regulation and predictive potential in cancer therapy.

Publications

Discrimination between circulating endothelial cells and blood cell populations with overlapping phenotype reveals distinct regulation and predictive potential in cancer therapy.

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