October 15 Cancer Research Highlights

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Selected Articles from the October 15, 2005 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 October 15 issue of Cancer Research.

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Wnt-5a Limits Tumor Migration, Marks Longer Survival

Dejmek et al.
Page 9142

Oncogenic Wnt/β-catenin signaling commonly occurs in colorectal cancers. In contrast, very little is known about the role of the nontransforming Wnt-5a. Dejmek et al. found that Wnt-5a expression was reduced or lost in 50% of Dukes B colorectal cancers. Wnt-5a negativity was shown to be a strong predictor of adverse outcome. Addition of recombinant Wnt-5a to Wnt-5a nonexpressing colon cancer cells reduced their migratory capacity. Consequently, Wnt-5a-expression in Dukes B colon cancer constitutes a good prognostic marker for longer survival, possibly explained by the ability of Wnt-5a to impair tumor cell migration and thus reduce invasiveness and metastasis.

 

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Amphiregulin, TGF-α Levels Predict Poor Response to Gefitinib

Ishikawa et al.
Page 9176

The presence of EGFR mutations can usually predict NSCLC patients likely to show partial response to gefitinib, but this approach requires acquisition of tissue specimens by surgery or biopsy, and has no power to indicate patients keeping stable condition who could also receive a survival benefit. Ishikawa et al. demonstrated that the survival time of gefitinib-treated NSCLC patients with positive values for serum amphiregulin or TGF-α was significantly shorter than for patients with negative values. Detecting the serum amphiregulin and TGF-α is a routinely feasible, relatively noninvasive, and significant predictor for poor response of advanced NSCLCs to gefitinib treatment.

 

 

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Multifunctional ADAM9 Key in Prostate Cancer Pathogenesis

Peduto et al.
Page 9312

ADAM9 is a membrane-anchored metalloprotease that is up-regulated in several human carcinomas and in mouse models for prostate, breast, and intestinal carcinoma. Peduto et al. report that “loss of function” experiments with Adam9–/– mice established a key role for ADAM9 in tumorigenesis in a mouse model for prostate cancer, and “gain of function” studies showed that mice overexpressing ADAM9 in prostate epithelium develop epithelial hyperplasia and prostatic intraepithelial neoplasia (PIN). Moreover, ADAM9 can release EGF and FGFR2iiib from cells, both of which have pivotal functions in prostate cancer. These results raise the possibility that ADAM9 might be a good target for antitumor drugs.

 

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Melanoma Cells Showing Stem Cell Properties Are Tumorigenic

Fang et al.
Page 9328

Tumors may contain a stem cell subpopulation that can self-renew to sustain tumor growth. To explore the existence of a stem cell subpopulation in melanoma, Fang et al. applied a novel culture technique to tumor specimens and cell lines. Selected melanoma cells proliferated as nonadherent spheres and showed the capacity for self-renewal. The melanoma spheres could differentiate into multiple lineages, including melanocytic, adipocytic, chondrocytic and osteocytic differentiation. Compared to adherent melanoma cells isolated and maintained under conventional culture conditions, melanoma cells with stem-cell properties were highly tumorigenic. They expressed CD20, allowing their targeting for therapy with specific antagonists.

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NGF Blocking Antibody Reduces Bone Cancer Pain

Halvorson et al.
Page 9426

Prostate tumors avidly metastasize to bone where they induce significant bone remodeling and pain. Halvorson et al. utilized an antibody to nerve growth factor (NGF) in a prostate model of bone cancer where significant bone formation and bone destruction occur simultaneously in the mouse femur. Administration of the blocking antibody to NGF produced a significant reduction in both early- and late-stage bone cancer pain–related behaviors equivalent to that achieved with acute administration of high doses of morphine. These data provide the rationale for an anti-NGF clinical trial for treating patients with bone pain due to metastatic prostate cancer.

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