This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our long-term goal is to understand how alterations in the composition of the extracellular matrix (ECM) affect the growth and metastasis of oral tumors and the formation of the vasculature that feeds tumors. It is well known that the interactions of transformed cells and their normal counterparts with specific ECM proteins are very different. In addition, the ECM produced by transformed cells is very different than normal ECM. Nevertheless, the abilities of specific ECM proteins to regulate tumor growth, metastasis, and angiogenesis in vivo are poorly understood. We have found that in active oral squamous cell carcinomas (SCC) the expression of ECM proteins, versican, neurocan, tenascin, periostin, and MMP-9, are highly up-regulated and some of them are present as altered molecular weights. We therefore propose the hypothesis that the lelvated expression of ECM in oral SCC plays a role in tumor growth, invasion, and angiogenesis. To test this hypothesis, we will use a murine oral SCC cell line (SCC VII/SF) and study that: i) how the altered ECM environment affects tumor cell migration and invasion, and if so ii) what type of intracellular signaling is responsible for them. To achieve these goals, we will genetically modify the SCC VII/SF cells to over-express or silence the expression of candidate ECM and then.perform migration or invasion assays in order to understand the impact of genetic modulation.
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