In Cancer Research this week, researchers at Case Western Reserve University report their discovery that the c-MYC gene can alter the response of human mammary epithelial cells to the cytokine oncostatin M. OSM is responsible for the activation of STAT3, which has been implicated in cancer development, progression, invasion, and metastasis. However, OSM has also been implicated in the suppression of certain tumor-derived cell lines. Using human mammary epithelial cells, the researchers found that OSM signaling suppressed c-MYC "and engaged a p16- and p53-independent growth arrest that required STAT3 activity." Additionally, the team found that "expression of c-MYC from a constitutive promoter also abrogated the STAT3-mediated arrest, and strikingly, cooperated with OSM to promote anchorage-independent growth, a property associated with malignant transformation." These results suggest that c-MYC may be an important molecular switch that alters cells to respond in a tumor-promoting way to OSM-mediated signaling.
Also in Cancer Research this week, researchers in the Netherlands say that chemotherapy can enhance metastasis formation in VEGFR-1-expressing endothelial cells. Using an experimental pulmonary metastasis mouse model, the researchers pretreated the animals with chemotherapy, and then administered tumor cells intravenously after the drugs had cleared the animals' circulatory systems. "Pretreatment with the commonly used chemotherapeutic agents cisplatin and paclitaxel significantly enhanced lung metastasis in this model," the authors write. "This corresponded to enhanced adhesion of tumor cells to an endothelial cell monolayer that had been pretreated with chemotherapy in vitro." In addition, the team found that chemotherapy exposure enhanced the expression of VEGFR-1 on endothelial cells both in vitro and in vivo, suggesting that the inhibition of VEGFR-1 function could be used to counteract chemotherapy-induced retention of tumor cells.
And finally in Cancer Research this week, researchers in Australia found that the oncogene MYB is essential for mammary tumorigenesis. Using models of human and murine breast cancer, the team found that MYB expression is important for both in vivo and in vitro tumor cell growth. "In transgenic knockout mice, tissue-specific deletion of the murine MYB gene caused a transient defect in mammary gland development that was reflected in delayed ductal branching and defective apical bud formation," the authors write. "In mouse mammary tumor virus (MMTV)-NEU mice where tumors are initiated by activation of HER2, MYB deletion was sufficient to abolish tumor formation."