July 15 Cancer Research Highlights

Circulating tumor cells (CTC) are emerging as a powerful prognostic and predictive biomarker in several types of cancer, including breast, colon, and prostate. Studies of CTC in metastasis and further development of CTC as a biomarker in cancer have been limited by the inability to repetitively monitor CTC in mouse models of cancer. Eliane and colleagues have validated a method to reproducibly recover and enumerate CTC in blood samples obtained from living mice, using a modified version of an in vitro diagnostic system for quantifying CTC in patients. They show that CTC are present in blood samples from mice bearing orthotopic xenografts of several different breast cancer cell lines and primary breast cancer cells from patient biopsies and demonstrate that this technology can be used for serial monitoring of CTC in mouse xenograft models of human breast cancer. These results establish a new method for studying CTC in mouse models of epithelial cancer, providing the foundation for studies of molecular regulation of CTC in cancer and CTC as a biomarker for therapeutic efficacy. 

 

The prognosis for malignant glioma remains dismal despite advances in neurosurgery, radiotherapy, and chemotherapy, with an estimated median survival of less than one year. Neurofibromatsis 2 syndrome is an inherited glioma malignancy characterized by the development of schwannomas, meningiomas, and a type of glioma called ependymomas. The role of merlin in schwannomas and meningiomas has been examined in numerous studies, but comparatively little is known about the function of merlin in glial cell tumors. Lau and colleagues show that merlin expression is dramatically reduced in human malignant gliomas and that re-expression of functional merlin potently inhibits subcutaneous and intracranial growth of human glioma cells in mice by inhibiting cell proliferation and promoting apoptosis. They also show that merlin results in the activation of the MST1/2-Lats 2 signaling pathway and inhibition of the canonical and noncanonical Wnt signaling pathways. Collectively, these results demonstrate that merlin is a potent inhibitor of high-grade human glioma.

Malignant melanoma is the most significant and potentially lethal human skin cancer. Both the incidence of melanoma and its associated mortality rate are increasing, and there is currently no effective long-term treatment. Phosphate and tensin homologue deleted on chromosome 10(PTEN) is a tumor suppressor gene inactivated in numerous sporadic cancers, including melanomas. To analyze Pten function in melanocytes, Inoue-Narita and colleagues used the Cre-loxP system to delete Pten specifically in murine pigment-producing cells and generated DctCrePten^flox/flox mice. When these mutant mice were subjected to repeated depilations, melanocyte stem cells in the bulge of the hair follicle resisted exhaustion and the mice were protected against hair graying. Although spontaneous melanomas did not form in DctCrePten^flox/flox mice, large nevi and melanomas developed after carcinogen exposure. DctCrePten^flox/flox melanocytes were increased in size and exhibited heightened activation of Akt and extracellular signal–regulated kinases, increased expression of Bcl-2, and decreased expression of p27^Kip1. These results show that Pten is important for the maintenance of melanocyte stem cells and the suppression of melanomagenesis.

Tumor Microstructure-Defined Temporal Diffusion Spectroscopy

Colvin et al.

Page 5941