Matrix stiffness-regulated cellular functions under different dimensionalities

Zhong, Jiajun; Yang, Yuexiong; Liao, Liqiong; Zhang, Chao

doi:10.1039/c9bm01809c

Cited by 52 publications

(48 citation statements)

References 186 publications

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“…In tumors, cells respond to the biochemical signals of their ECM, but also to physical forces such as tension (traction and compression forces that maintain their stability), known as biotensegrity [ 2 ]. In fact, increased stromal stiffness is a classic hallmark of cancer [ 1 , 5 ], as is transformation of this stiffness into chemical signals through mechanotransduction for cell advantage [ 5 – 7 ]. Data suggest that an aberrant ECM may promote genetic instability and can even compromise DNA repair pathways necessary to prevent malignant transformation [ 6 , 8 – 10 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of extracellular matrix stiffness on genomic heterogeneity in MYCN-amplified neuroblastoma cell line

López-Carrasco

Martín-Vañó

Burgos‐Panadero

et al. 2020

J Exp Clin Cancer Res

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Background Increased tissue stiffness is a common feature of malignant solid tumors, often associated with metastasis and poor patient outcomes. Vitronectin, as an extracellular matrix anchorage glycoprotein related to a stiff matrix, is present in a particularly increased quantity and specific distribution in high-risk neuroblastoma. Furthermore, as cells can sense and transform the proprieties of the extracellular matrix into chemical signals through mechanotransduction, genotypic changes related to stiffness are possible. Methods We applied high density SNPa and NGS techniques to in vivo and in vitro models (orthotropic xenograft vitronectin knock-out mice and 3D bioprinted hydrogels with different stiffness) using two representative neuroblastoma cell lines (the MYCN-amplified SK-N-BE(2) and the ALK-mutated SH-SY5Y), to discern how tumor genomics patterns and clonal heterogeneity of the two cell lines are affected. Results We describe a remarkable subclonal selection of genomic aberrations in SK-N-BE(2) cells grown in knock-out vitronectin xenograft mice that also emerged when cultured for long times in stiff hydrogels. In particular, we detected an enlarged subclonal cell population with chromosome 9 aberrations in both models. Similar abnormalities were found in human high-risk neuroblastoma with MYCN amplification. The genomics of the SH-SY5Y cell line remained stable when cultured in both models. Conclusions Focus on heterogeneous intratumor segmental chromosome aberrations and mutations, as a mirror image of tumor microenvironment, is a vital area of future research.

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Section: Introductionmentioning

confidence: 99%

Impact of extracellular matrix stiffness on genomic heterogeneity in MYCN-amplified neuroblastoma cell line

López-Carrasco

Martín-Vañó

Burgos‐Panadero

et al. 2020

J Exp Clin Cancer Res

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show abstract

“…In tumors, cells respond to the biochemical signals of their ECM, but also to physical forces such as tension (traction and compression forces that maintain their stability), known as biotensegrity [2]. In fact, increased stromal stiffness is a classic hallmark of cancer [1,5], as is transformation of this stiffness into chemical signals through mechanotransduction for cell advantage [5][6][7]. Data suggest that an aberrant ECM may promote genetic instability and can even compromise DNA repair pathways necessary to prevent malignant transformation [6,[8][9][10].…”

Section: Introductionmentioning

confidence: 99%

“…1). The SCAs pertaining to the SK-N-BE(2) cell line in chromosomes7,11,13,19, and 20 were either absent or were only observed in proportionally few cells in tumors from VN-KO mice(Fig 1). Finally, NCA of chromosome 18 turned into a SCA in P1 to P3 including 18pq-(pter-q22.2, 67Mb) with the nal fragment 18q(22.2-ter, 11 Mb) as a CNLOH(Fig.…”

mentioning

confidence: 99%

Impact of extracellular matrix stiffness on genomic heterogeneity in MYCN-amplified neuroblastoma cell line

López-Carrasco

Martín-Vañó

Burgos‐Panadero

et al. 2020

Preprint

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Background: Increased tissue stiffness is a common feature of malignant solid tumors, often associated with metastasis and poor patient outcomes. Vitronectin, as an extracellular matrix anchorage glycoprotein related to a stiff matrix, is present in a particularly increased quantity and specific distribution in high-risk neuroblastoma. Furthermore, as cells can sense and transform the proprieties of the extracellular matrix into chemical signals through mechanotransduction, genotypic changes related to stiffness are possible.Methods: We applied high density SNPa and NGS techniques to in vivo and in vitro models (orthotropic xenograft vitronectin knock-out mice and 3D bioprinted hydrogels with different stiffness) using two representative neuroblastoma cell lines (the MYCN-amplified SK-N-BE(2) and the ALK -mutated SH-SY5Y), to discern how tumor genomics patterns and clonal heterogeneity of the two cell lines are affected. Results: We describe a remarkable subclonal selection of genomic aberrations in SK-N-BE(2) cells grown in knock-out vitronectin xenograft mice that also emerged when cultured for long times in stiff hydrogels. In particular, we detected an enlarged subclonal cell population with chromosome 9 aberrations in both models. Similar abnormalities were found in human high-risk neuroblastoma with MYCN amplification. The genomics of the SH-SY5Y cell line remained stable when cultured in both models. Conclusions: Focus on heterogeneous intratumor segmental chromosome aberrations and mutations, as a mirror image of tumor microenvironment, is a vital area of future research.

show abstract

“…In tumors, cells respond to the biochemical signals of their ECM, but also to physical forces such as tension (traction and compression forces that maintain their stability), known as biotensegrity [2]. In fact, increased stromal stiffness is a classic hallmark of cancer [1,5], as is transformation of this stiffness into chemical signals through mechanotransduction for cell advantage [5][6][7]. Data suggest that an aberrant ECM may promote genetic instability and can even compromise DNA repair pathways necessary to prevent malignant transformation [6,[8][9][10].…”

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Impact of extracellular matrix properties on neuroblastoma genomic heterogeneity

López-Carrasco¹,

Martín-Vañó²,

Burgos‐Panadero³

et al. 2020

Preprint

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Background Increased tissue stiffness is a common feature of malignant solid tumors, often associated with metastasis and poor patient outcomes. Vitronectin, as an extracellular matrix anchorage glycoprotein related to a stiff matrix, is present in a particularly increased quantity and specific distribution in high-risk neuroblastoma. Furthermore, as cells can sense and transform the proprieties of the extracellular matrix into chemical signals through mechanotransduction, genotypic changes related to stiffness are possible. Methods We have applied high density SNPa and NGS techniques to in vivo and in vitro models (orthotropic xenograft vitronectin knock-out mice and 3D bioprinted hydrogels with different stiffness) using two representative neuroblastoma cell lines (the MYCN amplified SK-N-BE(2) and the ALK mutated SH-SY5Y), to discern how tumor genomics patterns and clonal heterogeneity of both cell lines are affected. Results We describe a remarkable subclonal selection of some genomic aberrations in SK-N-BE(2) cells grown in knock-out vitronectin xenograft mice that also emerged when cultured for long times in stiff hydrogels. Specially, we detected an enlarged subclonal cell population with chromosome 9 aberrations in both models. Similar abnormalities were found in human high-risk neuroblastoma with MYCN amplification. Genomics of the SH-SY5Y cell line remained stable when cultured in both models. Conclusions Focus on heterogeneous intratumor segmental chromosome aberrations and mutations, as a mirror image of tumor microenvironment, is a vital area of future research.

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Matrix stiffness-regulated cellular functions under different dimensionalities

Abstract: The microenvironments that cells encounter with in vitro.

Cited by 52 publications

References 186 publications

Impact of extracellular matrix stiffness on genomic heterogeneity in MYCN-amplified neuroblastoma cell line

Impact of extracellular matrix stiffness on genomic heterogeneity in MYCN-amplified neuroblastoma cell line

Impact of extracellular matrix stiffness on genomic heterogeneity in MYCN-amplified neuroblastoma cell line

Impact of extracellular matrix properties on neuroblastoma genomic heterogeneity

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