The brain microenvironment and cancer metastasis

Mol Cells. 2010 Aug;30(2):93-8. doi: 10.1007/s10059-010-0133-9. Epub 2010 Aug 19.

Abstract

The process of metastasis consists of a series of sequential, selective steps that few cells can complete. The outcome of cancer metastasis depends on multiple interactions between metastatic cells and homeostatic mechanisms that are unique to one or another organ microenvironment. The specific organ microenvironment determines the extent of cancer cell proliferation, angiogenesis, invasion and survival. Many lung cancer, breast cancer, and melanoma patients develop fatal brain metastases that do not respond to therapy. The blood-brain barrier is intact in and around brain metastases that are smaller than 0.25 mm in diameter. Although the blood-brain barrier is leaky in larger metastases, the lesions are resistant to many chemotherapeutic drugs. Activated astrocytes surround and infiltrate brain metastases. The physiological role of astrocytes is to protect against neurotoxicity. Our current data demonstrate that activated astrocytes also protect tumor cells against chemotherapeutic drugs.

MeSH terms

  • Animals
  • Apoptosis
  • Astrocytes / pathology
  • Blood-Brain Barrier / pathology
  • Brain Neoplasms / blood supply
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / secondary*
  • Disease Models, Animal
  • Humans
  • Neovascularization, Pathologic
  • Tumor Microenvironment*