April 15 Cancer Research Highlights

Selected Articles from the April 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 April 15 issue of Cancer Research.

Role of TM4SF1 in Angiogenesis

Shih et al.

Page 3272

Transmembrane-4-L-six-family-1 (TM4SF1) was originally described as a cancer cell protein associated with cell motility, invasion, and metastasis. Shih and colleagues now show that TM4SF1 is highly expressed on the surface of the vascular endothelial cells that line smooth muscle–coated blood vessels that supply several human cancers, including those in which the malignant cells themselves do not express TM4SF1. TM4SF1 was localized to the filopodia of cultured endothelial cells and knockdown prevented filopodia formation, inhibited cell mobility, blocked cytokinesis, and induced senescence. In vivo, TM4SF1 knockdown impaired the maturation of VEGF-A–induced blood vessels. TM4SF1 thus emerges as an important new player in endothelial cell biology and as a potential target for antiangiogenesis therapy.

ALDH1 Tracks Human Colonic Stem Cells during Colon Tumorigenesis

Huang et al.

Page 3382

Ascertaining the contribution of stem cells (SC) to the appearance and growth of colorectal cancer had been slowed by a lack of markers that identify and isolate normal and malignant SCs from the colon. Huang and colleagues identify aldehyde dehydrogenase (ALDH) as a specific marker for both normal and malignant colon SCs. ALDH1⁺ cells are sparse and restricted to the crypt bottom in normal epithelium, increasing in number and becoming distributed farther up the crypts during progression to adenoma. Implantation of ALDH⁺ colon carcinoma cells into immunodeficient mice generated xenograft tumors. These results support the hypothesis that SC overpopulation occurs during colonic tumorigenesis and drives the development of colorectal cancer.

Targeting Glioblastoma Cancer Stem Cells with Oncolytic HSV Vectors

Wakimoto et al.

Page 3472

The lack of glioma models that recapitulate the pathology of human glioblastoma has hindered the development of effective therapies. Wakimoto and colleagues established cancer stem cell–enriched expandable cultures from human glioblastoma specimens, which upon intracerebral implantation into mice reproducibly and efficiently formed tumors with the hallmarks of glioblastoma, including a highly invasive phenotype. Utilizing this model, the authors demonstrated that intratumoral injection of oncolytic herpes simplex virus vectors can target highly invasive cancer cells and lead to extended survival of animals, thereby underscoring the value of both the novel model system and the application of virotherapy for this deadly cancer.

GCC Immunotherapy without Colitis or Tumorigenesis

Snook et al.

Page 3537

Snook and colleagues explored the relationship between immunotherapy for systemic colon cancer metastasis and its effect on inflammatory bowel disease (IBD) and carcinogenesis in mice. Immunization of mice with the intestinal cancer mucosa antigen guanylyl cyclase C (GCC) elicited lineage-specific CD8⁺ T-cell responses protecting against systemic metastases, but spared the intestine from autoimmunity and failed to promote intestinal carcinogenesis induced by germ-line mutations or chronic inflammation. These observations support the utility of GCC-targeted immunotherapy in patients at risk for systemic metastases, including those with IBD, hereditary colorectal cancer syndromes, and sporadic colorectal cancer. Moreover, they suggest that preferential lineage-specific tolerance may be a critical mechanism in preventing autoimmunity in peripheral tissues.

Key Regulators in Integrin Signaling

Chen et al.

Page 3713
During tumor dissemination, integrin-mediated cell adhesion to and migration on the extracellular matrix (ECM) proteins are required for cancer cell survival and adaptation to the new microenvironment. Chen and colleagues profile the phosphoproteomic changes induced by the interactions of cell integrins with ECM and report that integrin-ECM interactions modulate phosphorylation of 513 peptides, corresponding to 357 proteins. Among them, 33 key signaling mediators were subjected to siRNA-based functional screening. Three novel kinases were identified for their critical role in cell adhesion and migration. Together, the authors reveal novel regulators for tumor cell adhesion and migration and present an integrin-modulated phosphorylation network for tumor cell-ECM protein interactions.

April 15 Cancer Research Highlights

Selected Articles from the April 15, 2009 Issue

Role of TM4SF1 in Angiogenesis

ALDH1 Tracks Human Colonic Stem Cells during Colon Tumorigenesis

Targeting Glioblastoma Cancer Stem Cells with Oncolytic HSV Vectors

GCC Immunotherapy without Colitis or Tumorigenesis

Key Regulators in Integrin Signaling

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