Site-specific metastasis: A cooperation between cancer cells and the metastatic microenvironment

Sivan Izraely, Isaac P. Witz*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


The conclusion derived from the information provided in this review is that disseminating tumor cells (DTC) collaborate with the microenvironment of a future metastatic organ site in the establishment of organ-specific metastasis. We review the basic principles of site-specific metastasis and the contribution of the cross talk between DTC and the microenvironment of metastatic sites (metastatic microenvironment [MME]) to the establishment of the organ-specific premetastatic niche; the targeted migration of DTC to the endothelium of the future organ-specific metastasis; the transmigration of DTC to this site and the seeding and colonization of DTC in their future MME. We also discuss the role played by DTC-MME interactions on tumor dormancy and on the differential response of tumor cells residing in different MMEs to antitumor therapy. Finally, we summarize some studies dealing with the effects of the MME on a unique site-specific metastasis—brain metastasis.

Original languageEnglish
Pages (from-to)1308-1322
Number of pages15
JournalInternational Journal of Cancer
Issue number6
StatePublished - 15 Mar 2021


FundersFunder number
James and Rita Leibman Endowment Fund for Cancer Research
Laboratory of Tumor Microenvironment & Metastasis Research
Sara and Natan Blutinger Foundation
Dr. Miriam and Sheldon G. Adelson Medical Research Foundation


    • brain metastasis
    • cancer
    • metastatic microenvironment
    • site-specific metastasis


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