Microregional extracellular matrix heterogeneity in brain modulates glioma cell invasion

Anita C. Bellail, Stephen B. Hunter, Daniel J. Brat, Chalet Tan, Erwin G. Van Meir

Research output: Contribution to journalReview article

350 Scopus citations

Abstract

The invasion of neoplastic cells into healthy brain tissue is a pathologic hallmark of gliomas and contributes to the failure of current therapeutic modalities (surgery, radiation and chemotherapy). Transformed glial cells share the common attributes of the invasion process, including cell adhesion to extracellular matrix (ECM) components, cell locomotion, and the ability to remodel extracellular space. However, glioma cells have the ability to invade as single cells through the unique environment of the normal central nervous system (CNS). The brain parenchyma has a unique composition, mainly hyaluronan and is devoid of rigid protein barriers composed of collagen, fibronectin and laminin. The integrins and the hyaluronan receptor CD44 are specific adhesion receptors active in glioma-ECM adhesion. These adhesion molecules play a major role in glioma cell-matrix interactions because the neoplastic cells use these receptors to adhere to and migrate along the components of the brain ECM. They also interact with the proteases secreted during glioma progression that degrade ECM allowing tumor cells to spread and diffusely infiltrate the brain parenchyma. The plasminogen activators (PAs), matrix metalloproteinases (MMPs) and lysosomal cysteine peptidases called cathepsins are also induced during the invasive process. Understanding the mechanisms of tumor cell invasion is critical as it plays a central role in glioma progression and failure of current treatment due to tumor recurrence from micro-disseminated disease. This review will focus on the impact of microregional heterogeneity of the ECM on glioma invasion in the normal adult brain and its modifications in tumoral brain.

Original languageEnglish (US)
Pages (from-to)1046-1069
Number of pages24
JournalInternational Journal of Biochemistry and Cell Biology
Volume36
Issue number6
DOIs
StatePublished - Jun 1 2004

Keywords

  • Adhesion molecules
  • Extracellular matrix
  • Glioma
  • Invasion
  • Proteases

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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