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2014 ; 15
(12
): 1243-53
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The extracellular matrix modulates the hallmarks of cancer
#MMPMID25381661
Pickup MW
; Mouw JK
; Weaver VM
EMBO Rep
2014[Dec]; 15
(12
): 1243-53
PMID25381661
show ga
The extracellular matrix regulates tissue development and homeostasis, and its
dysregulation contributes to neoplastic progression. The extracellular matrix
serves not only as the scaffold upon which tissues are organized but provides
critical biochemical and biomechanical cues that direct cell growth, survival,
migration and differentiation and modulate vascular development and immune
function. Thus, while genetic modifications in tumor cells undoubtedly initiate
and drive malignancy, cancer progresses within a dynamically evolving
extracellular matrix that modulates virtually every behavioral facet of the tumor
cells and cancer-associated stromal cells. Hanahan and Weinberg defined the
hallmarks of cancer to encompass key biological capabilities that are acquired
and essential for the development, growth and dissemination of all human cancers.
These capabilities include sustained proliferation, evasion of growth
suppression, death resistance, replicative immortality, induced angiogenesis,
initiation of invasion, dysregulation of cellular energetics, avoidance of immune
destruction and chronic inflammation. Here, we argue that biophysical and
biochemical cues from the tumor-associated extracellular matrix influence each of
these cancer hallmarks and are therefore critical for malignancy. We suggest that
the success of cancer prevention and therapy programs requires an intimate
understanding of the reciprocal feedback between the evolving extracellular
matrix, the tumor cells and its cancer-associated cellular stroma.
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