TY - JOUR
T1 - The interface stiffness and topographic feature dictate interfacial invasiveness of cancer spheroids
AU - Mao, Bin Hsu
AU - Nguyen Thi, Kim Mai
AU - Tang, Ming Jer
AU - Kamm, Roger D.
AU - Tu, Ting Yuan
N1 - Publisher Copyright:
© 2023 The Author(s). Published by IOP Publishing Ltd.
PY - 2023/1
Y1 - 2023/1
N2 - During cancer metastasis, tumor cells likely navigate, in a collective manner, discrete tissue spaces comprising inherently heterogeneous extracellular matrix microstructures where interfaces may be frequently encountered. Studies have shown that cell migration modes can be determined by adaptation to mechanical/topographic cues from interfacial microenvironments. However, less attention has been paid to exploring the impact of interfacial mechnochemical attributes on invasive and metastatic behaviors of tumor aggregates. Here, we excogitated a collagen matrix-solid substrate interface platform to investigate the afore-stated interesting issue. Our data revealed that stiffer interfaces stimulated spheroid outgrowth by motivating detachment of single cells and boosting their motility and velocity. However, stronger interfacial adhesive strength between matrix and substrate led to the opposite outcomes. Besides, this interfacial parameter also affected the morphological switch between migration modes of the detached cells and their directionality. Mechanistically, myosin II-mediated cell contraction, compared to matrix metalloproteinases-driven collagen degradation, was shown to play a more crucial role in the invasive outgrowth of tumor spheroids in interfacial microenvironments. Thus, our findings highlight the importance of heterogeneous interfaces in addressing and combating cancer metastasis.
AB - During cancer metastasis, tumor cells likely navigate, in a collective manner, discrete tissue spaces comprising inherently heterogeneous extracellular matrix microstructures where interfaces may be frequently encountered. Studies have shown that cell migration modes can be determined by adaptation to mechanical/topographic cues from interfacial microenvironments. However, less attention has been paid to exploring the impact of interfacial mechnochemical attributes on invasive and metastatic behaviors of tumor aggregates. Here, we excogitated a collagen matrix-solid substrate interface platform to investigate the afore-stated interesting issue. Our data revealed that stiffer interfaces stimulated spheroid outgrowth by motivating detachment of single cells and boosting their motility and velocity. However, stronger interfacial adhesive strength between matrix and substrate led to the opposite outcomes. Besides, this interfacial parameter also affected the morphological switch between migration modes of the detached cells and their directionality. Mechanistically, myosin II-mediated cell contraction, compared to matrix metalloproteinases-driven collagen degradation, was shown to play a more crucial role in the invasive outgrowth of tumor spheroids in interfacial microenvironments. Thus, our findings highlight the importance of heterogeneous interfaces in addressing and combating cancer metastasis.
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U2 - 10.1088/1758-5090/acaa00
DO - 10.1088/1758-5090/acaa00
M3 - Article
C2 - 36594698
AN - SCOPUS:85145492228
SN - 1758-5082
VL - 15
JO - Biofabrication
JF - Biofabrication
IS - 1
M1 - 015023
ER -