Three-dimensional context regulation of metastasis.

TitleThree-dimensional context regulation of metastasis.
Publication TypeJournal Article
Year of Publication2009
AuthorsErler JT, Weaver VM
JournalClin Exp Metastasis
Date Published2009
KeywordsCell Division, Collagen, Disease Progression, Homeostasis, Humans, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasms

Tumor progression ensues within a three-dimensional microenvironment that consists of cellular and non-cellular components. The extracellular matrix (ECM) and hypoxia are two non-cellular components that potently influence metastasis. ECM remodeling and collagen cross-linking stiffen the tissue stroma to promote transformation, tumor growth, motility and invasion, enhance cancer cell survival, enable metastatic dissemination, and facilitate the establishment of tumor cells at distant sites. Matrix degradation can additionally promote malignant progression and metastasis. Tumor hypoxia is functionally linked to altered stromal-epithelial interactions. Hypoxia additionally induces the expression of pro-migratory, survival and invasion genes, and up-regulates expression of ECM components and modifying enzymes, to enhance tumor progression and metastasis. Synergistic interactions between matrix remodeling and tumor hypoxia influence common mechanisms that maximize tumor progression and cooperate to drive metastasis. Thus, clarifying the molecular pathways by which ECM remodeling and tumor hypoxia intersect to promote tumor progression should identify novel therapeutic targets.

Alternate JournalClin. Exp. Metastasis
PubMed ID18814043
PubMed Central IDPMC2648515
Grant ListCA078731 / CA / NCI NIH HHS / United States
R01 CA078731-07 / CA / NCI NIH HHS / United States
T32 CA009151 / CA / NCI NIH HHS / United States
/ / Cancer Research UK / United Kingdom