American Association for Cancer Research

February 15 Cancer Research Highlights

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Selected Articles from the February 15, 2009 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 Imaging with ICG-Conjugated Antibody

Ogawa et al.

Page 1268

Tumor detection and characterization are important first steps to cancer therapy. Growing numbers of monoclonal antibodies have been approved for human use. Ogawa and colleagues have successfully developed activatable optical molecular imaging probes comprised of the FDA-approved near-infrared fluorophore indocyanine green and humanized antibodies which “switch on” only in the target cells.  The conjugates minimally fluoresced outside cells, yet strongly fluoresced within target cancer cells only after binding and internalization.  Using these probes, specific detection and characterization of tumors were achieved in vivo. These activatable probes have a high likelihood of translation into the clinical setting because the major components are already approved for use in humans. 
 

miR-146 Suppresses Breast Cancer Metastasis

Hurst et al.

Page 1279

Metastasis requires coordinated expression of pro- and antimetastatic genes. Breast cancer metastasis suppressor 1 (BRMS1) inhibits multiple steps of the metastatic cascade by regulating transcription of metastasis-associated genes, including noncoding RNA. Hurst and colleagues report that BRMS1 up-regulates miR-146a and miR-146b expression and that expression of either miR-146a or miR-146b in MDA-MB-231 breast carcinoma cells suppresses lung metastasis. These data show, for the first time, a connection between a metastasis suppressor and microRNA to regulate metastasis and a BRMS1–miR-146 axis targeting metastasis-associated genes at the levels of transcription and translation.


β1 Integrin Mutation

Ferreira et al.

Page 1334

Changes in the amino acid sequence of β integrin extracellular matrix receptors are found at low frequency in a range of tumors but their physiological relevance is unclear. One of these mutations, T188Ib1, has been associated with poorly differentiated squamous cell carcinoma. Ferreira and colleagues report that this mutant results in increased ligand binding of the β1 integrin subunit. The authors also show that this mutation does not affect normal skin architecture or homeostasis, but does increase the susceptibility of the epidermis to developing tumors and influences tumor type when expressed in the epidermis of transgenic mice. These findings demonstrate that tumor-associated integrin mutations and polymorphisms have the potential to influence cancer susceptibility and disease outcome.


Variation in genes affecting the bioavailability of vitamin E could impact prostate cancer risk. In a study of 982 incident prostate cancer cases and 851 matched controls drawn from a vitamin E supplementation trial, Wright and colleagues examined whether 13 variants in two key vitamin E transport genes, TTPA and SEC14L2, were associated with prostate cancer. Although no associations were observed, several variants in SEC14L2 modified the effect of the trial vitamin E supplementation on prostate cancer risk. These findings could have important implications regarding vitamin E use and the design, analysis, and interpretation of ongoing and future trials.     


MV-uPA Targets Tumor Vasculature

Jing et al.

Page 1459

Oncolytic viruses exert potent antitumor effects; however, the inability of viruses to cross the endothelial barrier limits intratumoral delivery. To circumvent this problem, Jing and colleagues engineered a novel oncolytic measles virus, MV-uPA, retargeted against the tumor and vascular target urokinase receptor (uPAR). MV-uPA induced cell fusion and cytotoxicity in an uPAR-specific manner and exerted potent in vivo antitumor effects. MV-uPA infected activated endothelial cells expressing higher uPAR more efficiently than nonactivated endothelial cells. Using a murine version of MV-uPA, the authors demonstrated successful viral transduction of murine mammary tumor and, for the first time, in vivo targeting of tumor capillaries. The ability of MV-uPA to target tumor cells and capillaries makes it a promising agent for the treatment of breast cancer and other malignancies.  


CCL2 Facilitates Prostate Cancer Growth in Bone

Li et al.

Page 1685

Monocyte chemoattractant protein 1 (CCL2) has been identified recently as a regulator of prostate cancer metastasis in the bone marrow microenvironment with CCL2 facilitating osteoclastogenesis and  stimulating prostate carcinoma cell growth. Li and colleagues report that prostate cancer–derived PTHrP elevates CCL2 levels in osteoblast-derived bone marrow by increasing osteoclastic bone resorption and facilitating prostate cancer growth in bone. The authors also found that CCL2 binds to its receptor on cancer cells and stimulates release of the proangiogenic factor VEGF-A to enhance neo-blood vessel formation. These results suggest that CCL2 facilitates metastatic tumor growth via activation of tumor cells, bone resorption, and angiogenesis. Targeting CCL2 could be a promising therapeutic strategy for prostate cancer skeletal metastasis. 


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