Non-invasive in vivo analysis of early metastatic processes

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For elucidating early phase of tumor metastasis, we developed non-invasive method to determine metastatic tumor cell trafficking by PET. We have already observed the correlation between metastatic potential and metastatic cell accumulation in a target tissues. In the present study, we firstly clarified the involvement of selectins in the early tumor cell trafficking. We also observed sulfatide, a ligand for selectins, suppressed tumor metastasis. Secondly, we investigated the role of integrins in tumor metastatic process by using integrin transfectants. CHO cells were transfected with a chain of integrins, I.e., α2, α3, α4, α6, α9 and av. PET analysis indicated that integrin αvβ1 and α4β1 enhanced tumor cell accumulation in a target tissue. Furthermore, useful evidences were obtained about involvement of integrin avb3 in liver metastasis. Thirdly, we investigated the role of immune surveillance on the suppression of tumor metastasis. If small number of tumor cells were injected in experimental metastatic model, metastasis was not observed due to removal of tumor cells from target by immune defense system. In fact, metastasis was observed in mice which were pretreated for the depletion of macrophages even when small number of tumor cells were injected. And, in this case, removal of tumor cells from target tissues was suppressed by the determination of PET. Therefore, we clearly demonstrated that macrophage play an important role for suppressing metastasis in the early stage of metastatic processes.