American Association for Cancer Research

February 1 Cancer Research Highlights

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Selected Articles from the February 1, 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 February 1 issue of Cancer Research.


Multiplexed Urine Biomarker Test Outperforms PSA Test

Laxman et al.

Page 645

Laxman et al. Biomarkers are urgently needed to supplement or potentially replace serum PSA testing due to its inadequate specificity. Emerging evidence suggests that monitoring the noncoding RNA transcript PCA3 in urine may be useful in detecting prostate cancer in patients with elevated PSA levels. Laxman and colleagues measured the expression of PCA3, GOLPH2, SPINK1, AMACR, TFF3, ERG and TMPRSS2:ERG fusion transcripts in urine sediments using quantitative PCR. They found that TMPRSS2:ERG fusion status and increased PCA3, GOLPH2, and SPINK1 transcript expression were significant predictors of a positive prostate cancer biopsy. The multiplexed model comprised of these biomarkers outperformed serum PSA or urine PCA3 alone in detecting prostate cancer. 
 

Loss of Lkb1 Provokes Highly Invasive Endometrial Cancer

Contreras et al.

Page 759

Mutations in the LKB1 tumor suppressor gene result in Peutz-Jeghers syndrome, an autosomal dominant condition characterized by hamartomatous polyps of the gastrointestinal tract, and a dramatically increased risk of epithelial malignancies at other sites, including the female reproductive tract. Contreras and co-investigators showed that female mice heterozygous for a null Lkb1 allele spontaneously develop highly invasive endometrial adeno­carcinomas. In human endometrial cancers, Lkb1 expression is inversely correlated with tumor grade and stage, implying that Lkb1 inactivation or down-regulation also contributes to endometrial cancer progression in women. This study shows that Lkb1 plays an important role in the malignant transformation of endometrium and that Lkb1 loss promotes a highly invasive phenotype. 


Vaccine Protects against Prostate Cancer

Garcia-Hernandez et al.

Page 861

Prostate stem cell antigen (PSCA) is an attractive antigen to target using therapeutic vaccines because of its overexpression in prostate cancer, especially in metastases, and its limited expression in other normal tissues. Studies reported by Garcia-Hernandez and colleagues offer evidence that a PSCA-based vaccine can induce long-term protection against prostate cancer development in the prostate cancer–prone TRAMP mouse model. PSCA-vaccinated TRAMP mice had a 90% survival rate at 12 months of age. In contrast, all control mice had succumbed to prostate cancer or had heavy tumor loads. Crucially, this long-term protective immune response was not associated with any measurable induction of autoimmunity, making it an attractive therapeutic vaccine candidate. 


The magnitude and breadth of the p53-specific T-cell repertoire may be restricted due to the ubiquitous expression of wild-type p53 in normal somatic tissues. In view of the importance of the CD4+ T-helper (Th) cell responses in effective antitumor immunity, Lauwen and colleagues analyzed and compared the p53-specific reactivity of this T-cell subset in p53+/+ and p53–/– C57Bl/6 mice. Immunization of p53–/– and p53+/+ mice with synthetic peptide vaccines comprising the identified epitopes induced equal levels of Th1 immunity in both mouse types. Their findings imply that the p53-specific CD4+ T-cell repertoire is not restricted by self-tolerance and thus may be fully available for the immunologic targeting of cancer. 


Stromal Fibroblasts Promote Pancreatic Cancer

Hwang et al.

Page 918

Hwang et al.The tumor-associated stroma is increasingly recognized to play an important role in tumor progression; however, relatively little is known about its contribution to pancreatic cancer, which is characterized by a very dense desmoplastic stroma. Hwang and colleagues isolated and immortalized primary pancreatic stellate cells from the stroma of human pancreatic cancer and found that stellate cell–conditioned media promoted pancreatic cancer cell progression in vitro. In an orthotopic mouse model of pancreatic cancer, pancreatic stellate cells co-injected with tumor cells resulted in increased tumor growth, metastasis, and initiation in a dose-dependent manner. Thus, secreted factors from pancreatic stromal fibroblasts may provide new targets for inhibiting pancreatic cancer growth and metastasis.  


Gene Expression Profiles of Prostate Tumors Differ in African-Americans and European-Americans

Wallace et al.

Page 927

Mortality rates from prostate cancer are significantly higher in African-Americans when compared with European-Americans. Differences in innate tumor biology may contribute to this survival health disparity. Wallace and colleagues compared the gene expression patterns of prostate tumors in these populations and observed numerous differences between African-American and European-American patients. Notably, several known metastasis-promoting genes were more highly expressed in African-Americans. Disease association and pathway analyses revealed a common relationship of the differently expressed transcripts with tumor immunobiology programs. Together, the data suggest the existence of a distinct tumor microenvironment in the two patient groups, which could partially account for this well established health disparity in prostate cancer survival. 


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