March 1 Cancer Research Highlights

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

Netrin-1 Differentiates Human Embryonal Carcinoma Cells

Netrin-1, a secreted neuronal guidance molecule, may affect early neuroectodermal differentiation in pluripotent cells. Mancino and colleagues report the effects Netrin-1 on the differentiation of human embryonal carcinoma (EC) cells. Netrin-1 was capable of negatively affecting cell migration of human EC cells and inducing a more neuronal-like phenotype. These effects are shown to be mediated via interaction of Netrin-1 with its receptor Neogenin and activation of the tyrosine phosphatase SHP-2. This interaction ultimately leads to the reduction in the expression of the stem cell–related factors Oct4, Nanog, and Cripto-1. 

Vitamin D Receptor Polymorphisms and Ovarian Cancer

PLK1 Targeting in Anaplastic Thyroid Carcinoma

Anaplastic thyroid carcinoma (ATC) is one of the fastest growing human solid tumors, spreading rapidly with an often fatal outcome. Polo-like kinase 1 (PLK1), a serine/threonine kinase and key regulator of mitotic progression, is highly expressed in ATC. Nappi and colleagues show that ATC cells are addicted to PLK1 activity. Inhibition of PLK1 by BI 2536 caused apoptosis directly from mitotic arrest in ATC cells, but not normal thyrocytes. Furthermore, PLK1-depleted cancer cells arrested in prometaphase with a 4N DNA content and displayed phosphohistone H3 foci and characteristic mitotic (Polo) spindle aberrations. These findings identify PLK1 as a potential target for the molecular therapy of ATC.

Regulatory T cells (Treg), a lymphocyte subset with regulatory properties, can inhibit antitumor immune responses. However, little is known about their biology and interactions with other immune cells within the tumor. Gobert and colleagues have discovered that Treg cells that infiltrate into human primary breast tumors negatively impact patient survival only when present in lymphoid aggregates, a pseudo-lymphoid structure surrounding the tumor bed. The recruitment of Treg cells to these structures is mediated by CCR4/CCL22 and they were found to colocalize with mature dendritic cells (DC) and lymphocytes. Unlike other T cells, the Treg cells were activated and proliferated in situ, likely through interactions with mature DC. This demonstrates that Treg cells dominate other T-cell responses in these lymphoid aggregates and explains their negative impact on patient outcome and identifies new potential targets for therapeutic intervention.