The metastatic microenvironment

Shelly Maman, Isaac P. Witz

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


Metastasis is the major killer of cancer patients. Although increased understanding of the metastatic process was achieved in recent years, the mechanisms underlying the progression of cancer cells to form site-specific metastasis are still awaiting complete elucidation. The current consensus is that circulating tumor cells disseminate into future metastatic sites and that these disseminated tumor cells form micrometastasis in these sites. The micrometastases remain in a state of dormancy in these sites until awakened to progress towards overt metastases. Whereas the evidence implicating chemokine-chemokine receptor interactions as the mechanism responsible for the targeted migration of tumor cells to future metastatic sites is quite strong, the mechanisms that maintain dormancy of disseminated tumor cells and the mechanisms that awaken these dormant micrometastases, driving their progression towards frank metastasis, are still obscure. It is clear, however, that the metastatic microenvironment plays a major role in these events. Three topics are discussed in this review: Mechanisms that are involved in the targeted migration of tumor cells to future metastatic sites; Specific molecular signatures expressed by metastases and micrometastases and interactions between metastatic and micrometastatic cells with the metastatic microenvironment. In reviewing these topics we focused on studies performed in our lab with neuroblatoma lung and melanoma brain metastasis.

Original languageEnglish
Title of host publicationThe Tumor Immunoenvironment
PublisherSpringer Netherlands
Number of pages24
ISBN (Electronic)9789400762176
ISBN (Print)940076216X, 9789400762169
StatePublished - 1 Jan 2013


  • Chemokines
  • Dormancy
  • Melanoma
  • Metastasis
  • Metastatic microenvironment
  • Micrometastasis
  • Molecular signature
  • Neuroblastoma
  • Site-specific metastasis
  • Tumor


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