May 15 Cancer Research Highlights

Selected Articles from the May 15, 2008 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.

Down-regulation of p57^Kip2 Induces Prostate Cancer in the Mouse

Jin et al.

Page 3601

p57^Kip2 has been considered a candidate tumor suppressor gene because of its location in the genome, biochemical activities, and imprinting status. Jin and colleagues report that decreased expression of p57^Kip2 occurs early in prostatic intraepithelial neoplasia (PIN) lesions and remains at low levels in human prostate cancer. The authors also provide evidence demonstrating that the prostates of p57^Kip2 knockout mice grafted into athymic nude mice develop PIN and adenocarcinoma. This mouse prostate cancer model is the first that is pathologically identical to human prostate adenocarcinoma. These findings suggest that p57^Kip2 is an important gene in prostate cancer tumorigenesis and may be a potential target gene for prostate cancer prevention and therapy.

Breast Cancer Survival Is Associated with Telomere Length in Peripheral Blood Cells

Svenson et al.

Page 3618

Previous studies have shown that shorter telomeres in blood are associated with increased risk for head and neck, bladder, lung, and renal cell cancers, as well as breast cancer in high-risk families. Svenson and colleagues analyzed relative telomere length in peripheral blood cells from 265 newly diagnosed breast cancer patients and 446 controls. In this study, the patient group displayed significantly longer telomeres compared with controls. Furthermore, it was shown that breast cancer risk increased with increasing telomere length. These results show that telomere length differs between breast cancer patients and control subjects and may be a potential target gene for prostate cancer prevention and therapy.

Targeting N-Cadherin to Enhance Cytotoxic Chemotherapy

Augustine et al.

Page 3777

Melanoma is characterized by a phenotype “switch” from E- to N-cadherin, which is associated with increased motility and invasiveness as well as decreased apoptosis. ADH-1 is a novel pentapeptide that disrupts N-cadherin adhesion. Augustine and colleagues found that that ADH-1, when used in combination with the regional chemotherapy drug melphalan, reduced tumor growth up to 30-fold over melphalan alone using a mouse model of regional therapy. Clinical phase I studies are now in progress in both the regional and systemic settings with combination ADH-1 and chemotherapy. New approaches such as targeting N-cadherin provide hope for improvement in chemotherapeutic treatment of metastatic melanoma.

The Soluble α Chain of IL-15 Receptor and Cancer

Badoual et al.

Page 3907

Clinical studies have shown a correlation between high intratumoral IL-15 concentrations and poor clinical outcome in patients with head and neck cancers. Badoual and colleagues report that increased serum sIL-15Rα (soluble alpha chain of IL-15 receptor) is also correlated with poor clinical outcome. Surprisingly, sIL-15Rα did not act in vitro as an IL-15 antagonist but rather as an enhancer of IL-15–induced proinflammatory cytokines (IL-6, IL-17, and TNFα) that may promote tumor progression. This new tumor evasion mechanism, based on amplification of the intratumoral inflammatory reaction, may be extended to other types of tumors that have been shown to release sIL-15Rα.

TGF-β Subverts Antitumor Immune Surveillance

Nam et al.

Page 3915
Nam et al.

Overexpression of immunosuppressive cytokines such as transforming growth factor β (TGF-β) is one strategy that tumors have developed to escape effective antitumor immune surveillance. Using mouse models of breast and colon cancer, Nam and colleagues have identified a novel mechanism by which TGF-β can subvert the normally protective CD8+ arm of the adaptive immune system so that it actively promotes tumorigenesis. TGF-β in the tumor microenvironment induces CD8+ cells to make IL-17, which then acts as a direct tumor cell survival factor. Through induction of this inappropriate immune response, TGF-β turns a key antitumor defense mechanism against the host.

May 15 Cancer Research Highlights

Selected Articles from the May 15, 2008 Issue

Down-regulation of p57^Kip2 Induces Prostate Cancer in the Mouse

Breast Cancer Survival Is Associated with Telomere Length in Peripheral Blood Cells

Targeting N-Cadherin to Enhance Cytotoxic Chemotherapy

The Soluble α Chain of IL-15 Receptor and Cancer

TGF-β Subverts Antitumor Immune Surveillance

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