Since it has been well established that circulating tumor cells are selectively and actively modified by the primary tumor before metastatic spread has even occurred [100], the vesicle-related function of both JAKMIP2 and VTI1b could be relevant for the tumor cells localized at the primary site, which need to prepare the future-tissue colonization through the establishment of the pre-metastatic niche. The gene discussed is JAKMIP2; the disease is neoplasm.