The extracellular matrix modulates the hallmarks of cancer.
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.
Department of Surgery, Center for Bioengineering and Tissue Regeneration UCSF, San Francisco, CA, USA.
Michael W
MW
Pickup
Department of Surgery, Center for Bioengineering and Tissue Regeneration UCSF, San Francisco, CA, USA.
Janna K
JK
Mouw
Department of Surgery, Center for Bioengineering and Tissue Regeneration UCSF, San Francisco, CA, USA Departments of Anatomy, Bioengineering and Therapeutic Sciences, UCSF, San Francisco, CA, USA Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research UCSF, San Francisco, CA, USA UCSF Helen Diller Comprehensive Cancer Center UCSF, San Francisco, CA, USA Valerie.Weaver@ucsfmedctr.org.
Valerie M
VM
Weaver
D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008954:Models, Biological; D009362:Neoplasm Metastasis / Q000473:pathology; D009369:Neoplasms / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism
ECM; hallmarks of cancer; mechanotransduction