@article {291, title = {The extracellular matrix: a dynamic niche in cancer progression.}, journal = {J Cell Biol}, volume = {196}, year = {2012}, month = {2012 Feb 20}, pages = {395-406}, abstract = {

The local microenvironment, or niche, of a cancer cell plays important roles in cancer development. A major component of the niche is the extracellular matrix (ECM), a complex network of macromolecules with distinctive physical, biochemical, and biomechanical properties. Although tightly controlled during embryonic development and organ homeostasis, the ECM is commonly deregulated and becomes disorganized in diseases such as cancer. Abnormal ECM affects cancer progression by directly promoting cellular transformation and metastasis. Importantly, however, ECM anomalies also deregulate behavior of stromal cells, facilitate tumor-associated angiogenesis and inflammation, and thus lead to generation of a tumorigenic microenvironment. Understanding how ECM composition and topography are maintained and how their deregulation influences cancer progression may help develop new therapeutic interventions by targeting the tumor niche.

}, keywords = {Disease Progression, Extracellular Matrix, Humans, Neoplasms}, issn = {1540-8140}, doi = {10.1083/jcb.201102147}, author = {Lu, Pengfei and Weaver, Valerie M and Werb, Zena} } @article {321, title = {Tumor microenvironment and progression.}, journal = {J Surg Oncol}, volume = {103}, year = {2011}, month = {2011 May 1}, pages = {468-74}, abstract = {

Tumor blood vessels are heterogeneous, of at least six distinct types, are induced primarily by vascular endothelial growth factor-A (VEGF-A), and provide a potentially useful therapeutic target. Breast cancer is characterized by changes in the microenvironment that result in altered tensional homeostasis. Also, breast cancers arise as the result of epigenetic as well as genetic changes. Tumor blood vessel pericytes result, in part, from bone marrow precursor cells, and VEGF is a negative regulator of glioblastoma tumor cell invasion.

}, keywords = {Angiogenesis Inhibitors, Breast Neoplasms, Disease Progression, Female, Humans, Molecular Targeted Therapy, Neoplasm Invasiveness, Neoplasms, Neovascularization, Pathologic, Tumor Microenvironment, Vascular Endothelial Growth Factor A}, issn = {1096-9098}, doi = {10.1002/jso.21709}, author = {Dvorak, Harold F and Weaver, Valerie M and Tlsty, Thea D and Bergers, Gabriele} } @article {386, title = {A tense situation: forcing tumour progression.}, journal = {Nat Rev Cancer}, volume = {9}, year = {2009}, month = {2009 Feb}, pages = {108-22}, abstract = {

Cells within tissues are continuously exposed to physical forces including hydrostatic pressure, shear stress, and compression and tension forces. Cells dynamically adapt to force by modifying their behaviour and remodelling their microenvironment. They also sense these forces through mechanoreceptors and respond by exerting reciprocal actomyosin- and cytoskeletal-dependent cell-generated force by a process termed \&$\#$39;mechanoreciprocity\&$\#$39;. Loss of mechanoreciprocity has been shown to promote the progression of disease, including cancer. Moreover, the mechanical properties of a tissue contribute to disease progression, compromise treatment and might also alter cancer risk. Thus, the changing force that cells experience needs to be considered when trying to understand the complex nature of tumorigenesis.

}, keywords = {Animals, Cell Transformation, Neoplastic, Cytoskeleton, Disease Progression, Gene Expression, Humans, Mechanotransduction, Cellular, Neoplasms, Neoplastic Processes, Stress, Mechanical}, issn = {1474-1768}, doi = {10.1038/nrc2544}, author = {Butcher, Darci T and Alliston, Tamara and Weaver, Valerie M} } @article {401, title = {Three-dimensional context regulation of metastasis.}, journal = {Clin Exp Metastasis}, volume = {26}, year = {2009}, month = {2009}, pages = {35-49}, abstract = {

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.

}, keywords = {Cell Division, Collagen, Disease Progression, Homeostasis, Humans, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasms}, issn = {1573-7276}, doi = {10.1007/s10585-008-9209-8}, author = {Erler, Janine T and Weaver, Valerie M} }