May 15 Cancer Research Highlights

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Selected Articles from the May 15, 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 15 issue of Cancer Research.

Rap1 Links Acinar Polarity with Tumorigenic Potential

Maintenance of apico-basal polarity in normal breast epithelial acini requires a balance between cell proliferation, cell death, and proper cell-cell and cell-extracellular matrix signaling. Aberrations in any of these processes can disrupt tissue architecture and initiate tumor formation. Rap1, a member of the Ras family of small GTPases, is activated in response to a number of extracellular stimuli, including growth factors, cytokines, and cell adhesion. Itoh et al. showed that Rap1 is a crucial element in organizing acinar structure and inducing lumen formation. Rap1 acts as a central regulator of breast architecture, with normal levels of activation instructing polarity during acinar morphogenesis, while increased activation induces tumor formation and progression to malignancy. 

Lung Cancer Side Population Stem Cells Characterized

Stem cells have been isolated by their ability to efflux Hoechst 33342 dye and are often referred to as the “side population” (SP). In this study, Ho et al. used flow cytometry and a Hoechst 33342 dye efflux assay to isolate and characterize SP cells from six human lung cancer cell lines. SP cells were enriched in tumor-initiating properties compared with non-SP cells, and had higher potential for invasiveness. The authors found evidence that SP cells could fully regenerate a heterogeneous population resembling the original. These findings indicate that SP cells (isolated in this manner from these lines) may represent an enriched source of lung tumor–initiating cells with stem cell properties and, moreover, may be an important target for effective therapy and a useful tool to investigate the tumorigenic process.

Extralymphatic Tumors Prepare Draining Lymph Nodes for Metastases

Metastases from distant tumor sites often develop in lymphoid organs. However, the immunological mechanism(s) allowing such invasion is not known, particularly because these organs are considered to be hostile to tumor cells. Preynat-Seauve et al. showed that primary extralymphatic tumors protected from rejection tumor cells which were implanted into lymph nodes. Mechanistically, this protection involved induction of T-cell anergy in draining lymph nodes via a cross-presentation process. Such distant cross-tolerization of tumor-specific CD8⁺ T cells may be a permissive determinant event leading to invasion of draining lymph nodes. These data suggest that metastatic tumor cells may not need to down-regulate their intrinsic immunogenicity in order to spread via the lymphatic system.

Evidence of Androgen Activity in the Prostate Despite Castration

A primary treatment for prostate cancer remains androgen deprivation. To determine the efficacy of chemical castration in suppressing prostatic androgen activity, Mostaghel et al. evaluated androgen levels and androgen-regulated gene expression in prostate tissues from men undergoing chemical castration regimens. Though treatment reduced tissue androgens by 75%, many androgen-responsive genes were not suppressed, with persistent expression of prostate-specific antigen and androgen receptor genes evident even after prolonged castration. Suboptimal suppression of tumoral androgen activity may account for treatment heterogeneity observed among patients, and may lead to early and widespread adaptive cellular changes supporting prostate tumor survival despite a low androgen environment.