Endothelial cells metabolically regulate breast cancer invasion toward a microvessel
Breast cancer metastasis is initiated by invasion of tumor cells into the collagen type I-rich stroma to reach adjacent blood vessels. Prior work has identified that metabolic plasticity is a key requirement of tumor cell invasion into collagen. However, it remains largely unclear how blood vessels...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
AIP Publishing LLC
2023-12-01
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| Series: | APL Bioengineering |
| Online Access: | http://dx.doi.org/10.1063/5.0171109 |
| _version_ | 1797366995178487808 |
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| author | Matthew L. Tan Niaa Jenkins-Johnston Sarah Huang Brittany Schutrum Sandra Vadhin Abhinav Adhikari Rebecca M. Williams Warren R. Zipfel Jan Lammerding Jeffrey D. Varner Claudia Fischbach |
| author_facet | Matthew L. Tan Niaa Jenkins-Johnston Sarah Huang Brittany Schutrum Sandra Vadhin Abhinav Adhikari Rebecca M. Williams Warren R. Zipfel Jan Lammerding Jeffrey D. Varner Claudia Fischbach |
| author_sort | Matthew L. Tan |
| collection | DOAJ |
| description | Breast cancer metastasis is initiated by invasion of tumor cells into the collagen type I-rich stroma to reach adjacent blood vessels. Prior work has identified that metabolic plasticity is a key requirement of tumor cell invasion into collagen. However, it remains largely unclear how blood vessels affect this relationship. Here, we developed a microfluidic platform to analyze how tumor cells invade collagen in the presence and absence of a microvascular channel. We demonstrate that endothelial cells secrete pro-migratory factors that direct tumor cell invasion toward the microvessel. Analysis of tumor cell metabolism using metabolic imaging, metabolomics, and computational flux balance analysis revealed that these changes are accompanied by increased rates of glycolysis and oxygen consumption caused by broad alterations of glucose metabolism. Indeed, restricting glucose availability decreased endothelial cell-induced tumor cell invasion. Our results suggest that endothelial cells promote tumor invasion into the stroma due, in part, to reprogramming tumor cell metabolism. |
| first_indexed | 2024-03-08T17:11:32Z |
| format | Article |
| id | doaj.art-1dee78ac32704267b4082f2d457d77af |
| institution | Directory Open Access Journal |
| issn | 2473-2877 |
| language | English |
| last_indexed | 2024-03-08T17:11:32Z |
| publishDate | 2023-12-01 |
| publisher | AIP Publishing LLC |
| record_format | Article |
| series | APL Bioengineering |
| spelling | doaj.art-1dee78ac32704267b4082f2d457d77af2024-01-03T19:58:04ZengAIP Publishing LLCAPL Bioengineering2473-28772023-12-0174046116046116-1710.1063/5.0171109Endothelial cells metabolically regulate breast cancer invasion toward a microvesselMatthew L. Tan0Niaa Jenkins-Johnston1Sarah Huang2Brittany Schutrum3Sandra Vadhin4Abhinav Adhikari5Rebecca M. Williams6Warren R. Zipfel7Jan Lammerding8Jeffrey D. Varner9Claudia Fischbach10 Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York 14853, USA Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York 14853, USA Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York 14853, USA Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York 14853, USA Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York 14853, USA Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York 14853, USA Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York 14853, USA Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York 14853, USA Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York 14853, USA Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York 14853, USA Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York 14853, USABreast cancer metastasis is initiated by invasion of tumor cells into the collagen type I-rich stroma to reach adjacent blood vessels. Prior work has identified that metabolic plasticity is a key requirement of tumor cell invasion into collagen. However, it remains largely unclear how blood vessels affect this relationship. Here, we developed a microfluidic platform to analyze how tumor cells invade collagen in the presence and absence of a microvascular channel. We demonstrate that endothelial cells secrete pro-migratory factors that direct tumor cell invasion toward the microvessel. Analysis of tumor cell metabolism using metabolic imaging, metabolomics, and computational flux balance analysis revealed that these changes are accompanied by increased rates of glycolysis and oxygen consumption caused by broad alterations of glucose metabolism. Indeed, restricting glucose availability decreased endothelial cell-induced tumor cell invasion. Our results suggest that endothelial cells promote tumor invasion into the stroma due, in part, to reprogramming tumor cell metabolism.http://dx.doi.org/10.1063/5.0171109 |
| spellingShingle | Matthew L. Tan Niaa Jenkins-Johnston Sarah Huang Brittany Schutrum Sandra Vadhin Abhinav Adhikari Rebecca M. Williams Warren R. Zipfel Jan Lammerding Jeffrey D. Varner Claudia Fischbach Endothelial cells metabolically regulate breast cancer invasion toward a microvessel APL Bioengineering |
| title | Endothelial cells metabolically regulate breast cancer invasion toward a microvessel |
| title_full | Endothelial cells metabolically regulate breast cancer invasion toward a microvessel |
| title_fullStr | Endothelial cells metabolically regulate breast cancer invasion toward a microvessel |
| title_full_unstemmed | Endothelial cells metabolically regulate breast cancer invasion toward a microvessel |
| title_short | Endothelial cells metabolically regulate breast cancer invasion toward a microvessel |
| title_sort | endothelial cells metabolically regulate breast cancer invasion toward a microvessel |
| url | http://dx.doi.org/10.1063/5.0171109 |
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