The tetraspanin CD81 protein increases melanoma cell motility by up-regulating metalloproteinase MT1-MMP expression through the pro-oncogenic Akt-dependent Sp1 activation signaling pathways.

Despite the importance of multiple tetraspanin proteins in cancer invasion and metastasis, little is known about the role and significance of tetraspanin CD81 in these processes. In the present study, we examined CD81 effects on melanoma cell invasiveness and metastasis. Transfection of CD81 into melanoma cells lacking endogenous CD81 expression significantly enhanced the migrating, invasive, and metastatic abilities of melanoma cells. Interestingly, membrane type 1 matrix metalloproteinase (MT1-MMP) expression was found in CD81-expressing melanoma cells but not in CD81-deficient cells. siRNA knockdown of CD81 in melanoma cells with endogenous CD81 demonstrated decreased MT1-MMP levels and cell motility. Notably, CD81-induced cell migration was abrogated by antibody blocking and siRNA knockdown of MT1-MMP, indicating that MT1-MMP is responsible for CD81-stimulated melanoma cell migration. Promoter analysis revealed an essential role of the Sp1 transcription factor in CD81-induced MT1-MMP transcription. We also demonstrate that the Sp1-activating Akt pathway is involved in adhesion-dependent CD81 signaling to induce MT1-MMP expression and cell motility. Importantly, human skin cancer tissue specimens displayed a positive correlation of CD81 with MT1-MMP expression levels and a close association of CD81 with malignant melanomas. Taken together, these results strongly suggest that CD81 stimulates melanoma cell motility by inducing MT1-MMP expression through the Akt-dependent Sp1 activation signaling pathway, leading to increased melanoma invasion and metastasis.

[Education of bioterrorism preparedness and response in healthcare-associated colleges--current status and learning objectives development].

OBJECTIVES: Bioterrorism (BT) preparedness and response plans are particularly important among healthcare workers who will be among the first involved in the outbreak situations. This study was conducted to evaluate the current status of education for BT preparedness and response in healthcare-related colleges/junior colleges and to develop learning objectives for use in their regular curricula. METHODS: We surveyed all medical colleges/schools, colleges/junior colleges that train nurses, emergency medical technicians or clinical pathologists, and 10% (randomly selected) of them that train general hygienists in Korea. The survey was conducted via mail from March to July of 2007. We surveyed 35 experts to determine if there was a consensus of learning objectives among healthcare workers. RESULTS: Only 31.3% of medical colleges/schools and 13.3% of nursing colleges/junior colleges had education programs that included BT preparedness and responses in their curricula. The most common reason given for the lack of BT educational programs was 'There is not much need for education regarding BT preparedness and response in Korea'. None of the colleges/junior colleges that train clinical pathologists, or general hygienists had an education program for BT response. After evaluating the expert opinions, we developed individual learning objectives designed specifically for educational institutions. CONCLUSIONS: There were only a few colleges/junior colleges that enforce the requirement to provide education for BT preparedness and response in curricula. It is necessary to raise the perception of BT preparedness and response to induce the schools to provide such programs.