September 15 Cancer Research Highlights

Perturbations in the TGF-β system are widespread in human cancers, but the actions of TGF-β are complex, and still poorly understood. TGF-β can function either as tumor suppressors or as pro-progression factors, depending on the specific context. Tang and colleagues used a breast cancer model system to show that TGF-β can function as a tumor suppressor through a novel mechanism that involves depleting the cancer stem cell population and promoting differentiation of the proliferative progeny. Understanding how TGF-β is involved in cancer progression will be critical for successful development of targeted therapeutics.

As more and more studies indicate localized centers as the primary site of B-CLL cell proliferation, the use of peripheral blood derived B-CLL cells may not be optimal to study issues related to B-CLL proliferation. Dürig and coauthors have described a novel xenograft model of CLL generated by infusion of human primary CLL cells into immunodeficient NOD/SCID mice. Their results suggest that this model reflects the heterogeneity and important clinical characteristics of the disease and thus may serve as a tool for preclinical drug testing and the investigation of the pathophysiology of CLL. 

Bone morphogenetic protein 7 (BMP7) counteracts physiological epithelial-to-mesenchymal transition (EMT), a process that is indicative of epithelial plasticity. Because EMT is involved in cancer, Buijs and colleagues investigated whether BMP7 plays a role in breast cancer growth and metastasis. Their data suggested that decreased BMP7 expression during carcinogenesis in the human breast contributes to the acquisition of a bone metastatic phenotype. Because exogenous BMP7 can still counteract the breast cancer growth at the primary site and in bone, BMP7 may represent a novel therapeutic molecule for repression of local and bone metastatic growth of breast cancer. 

For patients with solid tumors, the tolerance of surrounding tissues often limits the dose of radiation that can be delivered. Thus, agents that preferentially increase the cytotoxic effects of radiation towards tumor cells would significantly alter the therapeutic ratio and improve patient survival. Using a high-throughput, unbiased screening approach, Lally and colleagues identified 4’-bromo-3’-nitropropiophenone (NS-123) as a radiosensitizer of human glioma cells in vitro and in vivo. Their work demonstrates the potential of this cell-based, high-throughput screening method to identify novel radiosensitizers and suggests that NS-123 and similar nitrophenol compounds may be effective in antiglioma modalities. 

Multiple tobacco smoke–related premalignant and malignant lesions develop synchronously or metachronously in various organ sites including the oral cavity. Although the importance of endogenous factors (e.g., oncogenes) in regulating clonal migration is well established, little is known about the role of exogenous factors. Du and colleagues sought to elucidate the mechanism by which tobacco smoke stimulated the migration of cells through extracellular matrix (ECM). Their results suggest that chemicals in tobacco smoke can mimic the effects of oncogenes in regulating uPA-dependent cell invasion through ECM. These findings also strengthen the rationale for determining whether inhibitors of EGFR tyrosine kinase reduce the risk of tobacco smoke–related second primary tumors.