American Association for Cancer Research

February 15 Cancer Research Highlights

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Selected Articles from the February 15, 2006 Issue

The articles referenced in this Highlights section will be available online in HTML and PDF formats to all interested users at no charge until the next issue of Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the February 15 issue of Cancer Research.


Cancer Stem Cells: Ready for Prime Time?

Wicha et al. and Hill

Page 1883
Page 1891

A number of recent papers have reported data suggesting that cancer stem cells can be isolated from solid human cancers. Some of these papers have postulate that the isolation of such cells will allow the identification of specific molecular properties that can be targeted for therapeutic purposes. Reviews by Wicha et al. and by Hill present the potential paradigm shift that the cancer stem cell hypothesis offers, while calling for scrutiny and objectivity in examining existing experimental evidence on cancer-related stem cells. Hill discusses some of the many uncertainties, both theoretical and technical, in the interpretation of the current results. Whether a small proportion of tumor cells are specific cancer stem cells that can be successfully isolated from solid cancers remains uncertain, he cautions. Wicha et al. note that recent advances in stem cell biology have provided strong evidence for the cancer stem cell hypothesis, suggesting that many tumors arise in tissue stem or progenitor cells. Tumors are driven by a cellular subcomponent that retains key stem cell properties. Although the basic components of this hypothesis are not new, it represents a paradigm shift in the understanding of carcinogenesis and tumor cell biology. Furthermore, it has fundamental implications for the cancer risk assessment, early detection, prevention, and treatment.

 


Green Tea Induces Gene Profile Signature in Mice

Lu et al.
Page 1956

CAN 02-15-06 Lu 1956Green tea has been shown to be a potent chemopreventive agent against lung tumorigenesis in animal models. Treatment of A/J mice with either green tea (0.6% in water) or a defined green tea catechin extract (Polyphenon E) (2.0 g/kg in diet) inhibited lung tumor tumorigenesis. Lu et al. established a 17-gene–expression profile specific for exposure to effective doses of either green tea or Polyphenon E. This gene-expression signature was altered both in normal lungs and lung adenomas when mice were exposed to green tea or Polyphenon E. These experiments identified patterns of gene expressions that both offer clues for green tea’s potential mechanisms of action and provide a molecular signature specific for green tea exposure.

 

 


Foxm1 Deletion Diminishes Lung Tumor Cell Proliferation

Kim et al.
Page 2153

CAN 02-15-06 Kim 2153The proliferation-specific Foxm1 transcription factor regulates expression of cell-cycle genes essential for DNA replication and mitosis. To determine the role of Foxm1 in lung tumorigenesis in vivo, Kim et al. used interferon-inducible Mx-Cre recombinase transgene to delete mouse Foxm1 fl/fl-targeted allele prior to inducing lung tumors with urethane. Mx-Cre Foxm1–/– mice exhibited diminished proliferation of lung tumor cells causing a significant reduction in number and size of lung adenomas. Foxm1 expression was elevated in a majority of human lung cancers, suggesting that Foxm1 can be used as a potential target for diagnosis and/or treatment of lung cancer.

 


Breast Tumor PTHrP Content Associated with Reduced Metastasis, Mortality

Henderson et al.

Page 2250

CAN 02-15-06 Henderson 2250 In a prospective study with a median of 10 years’ follow-up of 526 consecutive patients with operable breast cancer, Henderson et al. evaluated the significance of positive parathyroid hormone-related protein (PTHrP) staining by immunohistology. Improved survival was observed for the 79% of patients with tumors that stained positively for PTHrP. Patients with PTHrP-positive primary tumors were less likely to develop bone metastases. PTHrP status was associated with estrogen receptor and menopausal status but was not significantly associated with tumor size, vascular invasion, tumor grade, or patient age. This study establishes that increased production of PTHrP in primary breast tumors is associated with reduced metastases at all sites, including bone, and is consequently associated with reduced mortality.