Dear Colleagues, 

Cancer progression is commonly separated into the processes of primary tumor growth and secondary metastasis. On the one hand, cancer cells have the ability to sustain unlimited proliferation and to favorably influence their microenvironment; on the other hand, malignant cells are able to spread from one primary tumor and invade a distant organ through multiple signaling mechanisms that form the “metastatic cascade”. There are various molecular and cellular mechanisms underlying the different steps of the metastatic cascade. including the epithelial-to-mesenchymal transition, invasion, anoikis, transport through vessels, the outgrowth of secondary tumors, and angiogenesis through neovascularization. The neovascularization of tumors is naturally leaking, a feature that would permit not only the passage of tumor cells into the circulation, but also their entry from the circulation back into the tumor. Circulating tumor cells would probably need no additional adaptation to prosper in the microenvironment of their source tumor. They re-infiltrate an established tumor, enriching it with aggressive cells—a process known as “tumor self-seeding”. Self-seeding mechanisms provide us with prospects to explore new-targeted therapies that may perhaps interfere with slow or even prevent tumor progression. The process of cancer self-seeding sheds light on clinical observations, such as the relationship between the tumor size, prognosis, and local relapse. Such relationships may essentially be caused by the ability of aggressive cancer cells to self-seed, promoting both local tumor growth and distant metastases by similar mechanisms.

In this Special Issue, we aim to comprehensively describe “tumor self-seeding” mechanisms and explore how the circulating tumor cells, which are widely understood to be the seeds of metastasis, could represent an effective approach towards limiting the expansion of secondary lesions, as well as how targeting this stage of metastatic spreading may provide a potential therapeutic approach.

Dr. Paul Costeas
Guest Editor

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• cancer
• metastasis
• self-seeding mechanisms
• EMT
• angiogenesis
• hallmarks