DIFFERENTIAL SIGNALING OF CCR7 THROUGH ITS 2 ENDOGENOUS LIGANDS, CCL19 & CCL21

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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. The C-C chemokine receptor 7 (CCR7) regulates trafficking of na¿ve thymocytes during T cell development and during localization of T cells to and within lymph nodes. To develop an in vivo model to understand the signaling of CCR7 that controls migration of cells, we developed a metasis model. CCR7, which is also normally expressed at low levels in breast epithelia is up-regulated in certain breast cancers, however, the role of this up-regulation in tumor development/metastasis remains unclear. To define the role for CCR7 in metastasis we worked to develop two mouse models. To understand whether early expression of CCR7 during tumor development could block tumor metastasis, we generated a tetracycline regulatable CCR7 expression vector that was fused at the N-terminus to myc. This vector was to be used in two cell lines that are syngeneic with C57/Bl6 mice; the highly metastatic 4T07 and as a the non-metastatic 67NR cell lines. To determine if CCR7 could change the migration efficiency or targeting of a line that had a predictable metastatic behavior, we overexpressed constitutively activated CCR7 in the the PyVMT cells that reportedly migrate only to the lungs. PyVMT cells are syngeneic with FVB mice. Following a request by our LAR facility, all mice were pre-treated with aspirin, as a prophylactic measure for pain, prior to tumor injections. Although the mice were injected with 5 x105 tumor cells, and these mouse models characteristically develop tumors within 28 days only 8 of the 137 injected mice developed tumors at the injection site over a one year period. The development of tumors did not correlate with expression of CCR7.