TY - JOUR
T1 - Multicellular tumor invasion and plasticity in biomimetic materials
AU - Leggett, Susan E.
AU - Khoo, Amanda S.
AU - Wong, Ian Y.
N1 - Funding Information:
The authors gratefully acknowledge support from NIEHS through the T32 Training Grant in Environmental Pathology (5T32ES007272-25), NIGMS through the COBRE Center for Cancer Research Development at Rhode Island Hospital (1P30GM110759-01A1), a Rhode Island Foundation Medical Research Grant (20144137), as well as Start-Up Funds from Brown University.
Publisher Copyright:
© 2017 The Royal Society of Chemistry.
PY - 2017/8
Y1 - 2017/8
N2 - Cancer cell invasion through the extracellular matrix is associated with metastatic spread and therapeutic resistance. In carcinomas, the detachment and dissemination of individual cells has been associated with an epithelial-mesenchymal transition, but tumors can also invade using collective, multicellular phenotypes. This malignant tumor progression is also associated with alignment and stiffening of the surrounding extracellular matrix. Historically, tumor invasion has been investigated using 2D monolayer culture, small animal models or patient histology. These assays have been complemented by the use of natural biomaterials such as reconstituted basement membrane and collagen I. More recently, engineered materials with well-defined physical, chemical and biomolecular properties have enabled more controlled microenvironments. In this review, we highlight recent developments in multicellular tumor invasion based on microfabricated structures or hydrogels. We emphasize the role of interfacial geometries, biomaterial stiffness, matrix remodeling, and co-culture models. Finally, we discuss future directions for the field, particularly integration with precision measurements of biomaterial properties and single cell heterogeneity, standardization and scale-up of these platforms, as well as integration with patient-derived samples.
AB - Cancer cell invasion through the extracellular matrix is associated with metastatic spread and therapeutic resistance. In carcinomas, the detachment and dissemination of individual cells has been associated with an epithelial-mesenchymal transition, but tumors can also invade using collective, multicellular phenotypes. This malignant tumor progression is also associated with alignment and stiffening of the surrounding extracellular matrix. Historically, tumor invasion has been investigated using 2D monolayer culture, small animal models or patient histology. These assays have been complemented by the use of natural biomaterials such as reconstituted basement membrane and collagen I. More recently, engineered materials with well-defined physical, chemical and biomolecular properties have enabled more controlled microenvironments. In this review, we highlight recent developments in multicellular tumor invasion based on microfabricated structures or hydrogels. We emphasize the role of interfacial geometries, biomaterial stiffness, matrix remodeling, and co-culture models. Finally, we discuss future directions for the field, particularly integration with precision measurements of biomaterial properties and single cell heterogeneity, standardization and scale-up of these platforms, as well as integration with patient-derived samples.
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U2 - 10.1039/c7bm00272f
DO - 10.1039/c7bm00272f
M3 - Review article
C2 - 28530743
AN - SCOPUS:85026291051
SN - 2047-4830
VL - 5
SP - 1460
EP - 1479
JO - Biomaterials Science
JF - Biomaterials Science
IS - 8
ER -