A Relatively Small Gradient of Extracellular pH Directs Migration of MDA-MB-231 Cells In Vitro
Hematogenous tumor metastasis begins with the invasion and spread of primary tumor cells in the local tissue leading to intravasation. We hypothesized that tumor cells might actively migrate toward intratumor vessels with the extracellular metabolic gradient acting as a guiding cue. Here, we determi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/7/2565 |
| _version_ | 1797571242085056512 |
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| author | Eiji Takahashi Daisuke Yamaguchi Yoshihisa Yamaoka |
| author_facet | Eiji Takahashi Daisuke Yamaguchi Yoshihisa Yamaoka |
| author_sort | Eiji Takahashi |
| collection | DOAJ |
| description | Hematogenous tumor metastasis begins with the invasion and spread of primary tumor cells in the local tissue leading to intravasation. We hypothesized that tumor cells might actively migrate toward intratumor vessels with the extracellular metabolic gradient acting as a guiding cue. Here, we determined in vitro whether the extracellular gradient of pH can act as a cue for directional migration in MDA-MB-231 cells. Cell migration was determined by the wound-healing assay under gradients of extracellular pH (~0.2 units/mm) and oxygen concentration (~6% O<sub>2</sub>/mm) that were produced by a microfluidic device, gap cover glass (GCG). Without GCG, the migration of cells was spatially homogeneous; the same number of cells migrated to the rectangular wound space from the left and right boundaries. In contrast, when GCG generated pH/O<sub>2</sub> gradients across the wound space, the number of cells migrating to the wound space from the boundary with higher pH/O<sub>2</sub> values was considerably decreased, indicating a preferential movement of cells toward the region of higher pH/O<sub>2</sub> in the gradient. The addition of hepes in the extracellular medium abolished both the extracellular pH gradient and the directional cell migration under GCG. We conclude that relatively small gradients of pH in the extracellular medium compared to those found in Na<sup>+</sup>/H<sup>+</sup> exchanger-driven cell migration were sufficient to guide MDA-MB-231 cells. The directional cell migration as guided by the metabolic gradient could effectively elevate the probability of intravasation and, ultimately, hematogenous metastasis. |
| first_indexed | 2024-03-10T20:36:33Z |
| format | Article |
| id | doaj.art-2ab4c19fe8ff45fcba9b9f751b239cb7 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T20:36:33Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2ab4c19fe8ff45fcba9b9f751b239cb72023-11-19T20:56:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-04-01217256510.3390/ijms21072565A Relatively Small Gradient of Extracellular pH Directs Migration of MDA-MB-231 Cells In VitroEiji Takahashi0Daisuke Yamaguchi1Yoshihisa Yamaoka2Graduate School of Advanced Health Sciences, Saga University, Honjyo Machi 1, Saga 840-8502, JapanGraduate School of Advanced Health Sciences, Saga University, Honjyo Machi 1, Saga 840-8502, JapanGraduate School of Advanced Health Sciences, Saga University, Honjyo Machi 1, Saga 840-8502, JapanHematogenous tumor metastasis begins with the invasion and spread of primary tumor cells in the local tissue leading to intravasation. We hypothesized that tumor cells might actively migrate toward intratumor vessels with the extracellular metabolic gradient acting as a guiding cue. Here, we determined in vitro whether the extracellular gradient of pH can act as a cue for directional migration in MDA-MB-231 cells. Cell migration was determined by the wound-healing assay under gradients of extracellular pH (~0.2 units/mm) and oxygen concentration (~6% O<sub>2</sub>/mm) that were produced by a microfluidic device, gap cover glass (GCG). Without GCG, the migration of cells was spatially homogeneous; the same number of cells migrated to the rectangular wound space from the left and right boundaries. In contrast, when GCG generated pH/O<sub>2</sub> gradients across the wound space, the number of cells migrating to the wound space from the boundary with higher pH/O<sub>2</sub> values was considerably decreased, indicating a preferential movement of cells toward the region of higher pH/O<sub>2</sub> in the gradient. The addition of hepes in the extracellular medium abolished both the extracellular pH gradient and the directional cell migration under GCG. We conclude that relatively small gradients of pH in the extracellular medium compared to those found in Na<sup>+</sup>/H<sup>+</sup> exchanger-driven cell migration were sufficient to guide MDA-MB-231 cells. The directional cell migration as guided by the metabolic gradient could effectively elevate the probability of intravasation and, ultimately, hematogenous metastasis.https://www.mdpi.com/1422-0067/21/7/2565metastasiscell migrationpH gradientoxygen gradientMDA-MB-231 cells |
| spellingShingle | Eiji Takahashi Daisuke Yamaguchi Yoshihisa Yamaoka A Relatively Small Gradient of Extracellular pH Directs Migration of MDA-MB-231 Cells In Vitro International Journal of Molecular Sciences metastasis cell migration pH gradient oxygen gradient MDA-MB-231 cells |
| title | A Relatively Small Gradient of Extracellular pH Directs Migration of MDA-MB-231 Cells In Vitro |
| title_full | A Relatively Small Gradient of Extracellular pH Directs Migration of MDA-MB-231 Cells In Vitro |
| title_fullStr | A Relatively Small Gradient of Extracellular pH Directs Migration of MDA-MB-231 Cells In Vitro |
| title_full_unstemmed | A Relatively Small Gradient of Extracellular pH Directs Migration of MDA-MB-231 Cells In Vitro |
| title_short | A Relatively Small Gradient of Extracellular pH Directs Migration of MDA-MB-231 Cells In Vitro |
| title_sort | relatively small gradient of extracellular ph directs migration of mda mb 231 cells in vitro |
| topic | metastasis cell migration pH gradient oxygen gradient MDA-MB-231 cells |
| url | https://www.mdpi.com/1422-0067/21/7/2565 |
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