May 1 Cancer Research Highlights

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Selected Articles from the May 1, 2007 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 May 1 issue of Cancer Research.

Glioblastoma Cancer Stem Cells Characterized into Subtypes

The biological behavior and prognosis of glioblastomas vary considerably despite the absence of apparent histological differences. CD133⁺ cancer stem cells (CSC) in glioblastomas have been described only recently and provided a new paradigm in brain tumor biology. Beier et al. tested the hypothesis that glioblastomas might be divided into different subtypes according to different CSC properties. Neural stem cell-like cells in secondary glioblastomas were not detected, whereas primary glioblastomas either were driven by the recently described CD133⁺ CSCs or previously unknown CD133^– CSCs. The two subtypes of CSC not only fulfill functional stem cell criteria, but are also characterized by a distinct molecular profile, a specific growth pattern in vitro, and different proliferation indices in vivo. 

CD34 Required for Skin Tumor Development

The cell surface glycoprotein CD34 is uniquely expressed on stem cells in the mouse hair follicle bulge region, which are a major target of carcinogens in the two-stage model of skin carcinogenesis. Trempus et al. tested whether CD34 plays a functional role in skin tumor development using a CD34 knockout mouse model. The knockout mice exhibited a significant impairment in tumor-forming capacity, and hair follicle cycling was perturbed during tumor promotion. This study highlights the role of the stem cell in skin tumor development and yields insight into stem cell and hair follicle response to environmental stresses.

Her-2 Status Increases Breast Cancer Cell Growth in the Brain

Retrospective studies of breast cancer patients suggest that primary tumor Her-2 overexpression or trastuzumab therapy are associated with a devastating complication: the development of central nervous system (brain) metastases. By using a unique mouse model of brain metastases and the largest cohort of resected brain metastases of breast cancer to date, Palmieri et al. have provided evidence for a role for Her-2 in site-specific metastatic outgrowth in the brain. These data are significant because the incidence of metastases to the brain is increasing in women with breast cancer, particularly in those with Her-2–overexpressing tumors and in those receiving trastuzumab. The study has significant implications for patient treatment and monitoring, and for the need to design targeted therapies that can cross the blood-brain barrier.

Bystander Cells Show Post-Irradiation Instability

The “radiation-induced bystander effect”, in which irradiated cells can induce genomic instability in unirradiated neighboring cells, has important implications for cancer radiotherapy, diagnostic radiology, and human health. Sedelnikova et al. examined α-particle microbeam irradiation–induced bystander effects in human tissue models, which preserve the three-dimensional geometric arrangement and communication of cells present in tissues in vivo. Their findings demonstrate the involvement of DNA double-strand breaks (DSBs) in tissue bystander responses, and support the notion that bystander DNA DSBs are precursors to widespread downstream effects in human tissues. Bystander cells exhibiting post-irradiation signs of genomic instability may be more prone than unaffected cells to become cancerous, underscoring the importance of considering the indirect biological effects of radiation in cancer risk assessment.

Bexarotene Overcomes Gemcitabine Resistance in Lung Cancer

Drug resistance to chemotherapeutic agents is a major obstacle in cancer therapy and amplification of resistance genes. Tooker et al. evaluated the ability of bexarotene to modulate the acquisition and maintenance of gemcitabine resistance in Calu3 non–small-cell lung cancer models. In the prevention model, Calu3 cells treated repeatedly with gemcitabine alone gradually developed resistance. Their data indicate that bexarotene can resensitize gemcitabine-resistant tumor cells by reversing gene amplification. This suggests that bexarotene may have clinical utility in cancers in which drug-resistance by gene amplification is a major obstacle to successful therapy.