Impact of extracellular matrix stiffness on genomic heterogeneity in MYCN-amplified neuroblastoma cell line
Abstract 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 spec...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-10-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13046-020-01729-1 |
| _version_ | 1811315308343853056 |
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| author | Amparo López-Carrasco Susana Martín-Vañó Rebeca Burgos-Panadero Ezequiel Monferrer Ana P. Berbegall Beatriz Fernández-Blanco Samuel Navarro Rosa Noguera |
| author_facet | Amparo López-Carrasco Susana Martín-Vañó Rebeca Burgos-Panadero Ezequiel Monferrer Ana P. Berbegall Beatriz Fernández-Blanco Samuel Navarro Rosa Noguera |
| author_sort | Amparo López-Carrasco |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-13T11:27:57Z |
| format | Article |
| id | doaj.art-cd3c750eb176420b92fb8407516ded73 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-04-13T11:27:57Z |
| publishDate | 2020-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-cd3c750eb176420b92fb8407516ded732022-12-22T02:48:38ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662020-10-0139111310.1186/s13046-020-01729-1Impact of extracellular matrix stiffness on genomic heterogeneity in MYCN-amplified neuroblastoma cell lineAmparo López-Carrasco0Susana Martín-Vañó1Rebeca Burgos-Panadero2Ezequiel Monferrer3Ana P. Berbegall4Beatriz Fernández-Blanco5Samuel Navarro6Rosa Noguera7Department of Pathology, Medical School, University of Valencia/INCLIVADepartment of Pathology, Medical School, University of Valencia/INCLIVADepartment of Pathology, Medical School, University of Valencia/INCLIVADepartment of Pathology, Medical School, University of Valencia/INCLIVADepartment of Pathology, Medical School, University of Valencia/INCLIVADepartment of Pathology, Medical School, University of Valencia/INCLIVADepartment of Pathology, Medical School, University of Valencia/INCLIVADepartment of Pathology, Medical School, University of Valencia/INCLIVAAbstract 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.http://link.springer.com/article/10.1186/s13046-020-01729-1BiotensegrityClonal selectionStiffnessVitronectinXenograft3D-bioprinting |
| spellingShingle | Amparo López-Carrasco Susana Martín-Vañó Rebeca Burgos-Panadero Ezequiel Monferrer Ana P. Berbegall Beatriz Fernández-Blanco Samuel Navarro Rosa Noguera Impact of extracellular matrix stiffness on genomic heterogeneity in MYCN-amplified neuroblastoma cell line Journal of Experimental & Clinical Cancer Research Biotensegrity Clonal selection Stiffness Vitronectin Xenograft 3D-bioprinting |
| title | Impact of extracellular matrix stiffness on genomic heterogeneity in MYCN-amplified neuroblastoma cell line |
| title_full | Impact of extracellular matrix stiffness on genomic heterogeneity in MYCN-amplified neuroblastoma cell line |
| title_fullStr | Impact of extracellular matrix stiffness on genomic heterogeneity in MYCN-amplified neuroblastoma cell line |
| title_full_unstemmed | Impact of extracellular matrix stiffness on genomic heterogeneity in MYCN-amplified neuroblastoma cell line |
| title_short | Impact of extracellular matrix stiffness on genomic heterogeneity in MYCN-amplified neuroblastoma cell line |
| title_sort | impact of extracellular matrix stiffness on genomic heterogeneity in mycn amplified neuroblastoma cell line |
| topic | Biotensegrity Clonal selection Stiffness Vitronectin Xenograft 3D-bioprinting |
| url | http://link.springer.com/article/10.1186/s13046-020-01729-1 |
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