Characterizing the Motility of Chemotherapeutics-Treated Acute Lymphoblastic Leukemia Cells by Time-Lapse Imaging
Drug resistance is an obstacle in the therapy of acute lymphoblastic leukemia (ALL). Whether the physical properties such as the motility of the cells contribute to the survival of ALL cells after drug treatment has recently been of increasing interest, as they could potentially allow the metastasis...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-06-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/9/6/1470 |
| _version_ | 1827714965515010048 |
|---|---|
| author | Hsiao-Chuan Liu Eun Ji Gang Hye Na Kim Yongsheng Ruan Heather Ogana Zesheng Wan Halvard Bönig K. Kirk Shung Yong-Mi Kim |
| author_facet | Hsiao-Chuan Liu Eun Ji Gang Hye Na Kim Yongsheng Ruan Heather Ogana Zesheng Wan Halvard Bönig K. Kirk Shung Yong-Mi Kim |
| author_sort | Hsiao-Chuan Liu |
| collection | DOAJ |
| description | Drug resistance is an obstacle in the therapy of acute lymphoblastic leukemia (ALL). Whether the physical properties such as the motility of the cells contribute to the survival of ALL cells after drug treatment has recently been of increasing interest, as they could potentially allow the metastasis of solid tumor cells and the migration of leukemia cells. We hypothesized that chemotherapeutic treatment may alter these physical cellular properties. To investigate the motility of chemotherapeutics-treated B-cell ALL (B-ALL) cells, patient-derived B-ALL cells were treated with chemotherapy for 7 days and left for 12 h without chemotherapeutic treatment. Two parameters of motility were studied, velocity and migration distance, using a time-lapse imaging system. The study revealed that compared to non-chemotherapeutically treated B-ALL cells, B-ALL cells that survived chemotherapy treatment after 7 days showed reduced motility. We had previously shown that Tysabri and P5G10, antibodies against the adhesion molecules integrins α4 and α6, respectively, may overcome drug resistance mediated through leukemia cell adhesion to bone marrow stromal cells. Therefore, we tested the effect of integrin α4 or α6 blockade on the motility of chemotherapeutics-treated ALL cells. Only integrin α4 blockade decreased the motility and velocity of two chemotherapeutics-treated ALL cell lines. Interestingly, integrin α6 blockade did not affect the velocity of chemoresistant ALL cells. This study explores the physical properties of the movements of chemoresistant B-ALL cells and highlights a potential link to integrins. Further studies to investigate the underlying mechanism are warranted. |
| first_indexed | 2024-03-10T19:08:56Z |
| format | Article |
| id | doaj.art-30672be8be56480c9375232af11d1257 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T19:08:56Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-30672be8be56480c9375232af11d12572023-11-20T03:57:28ZengMDPI AGCells2073-44092020-06-0196147010.3390/cells9061470Characterizing the Motility of Chemotherapeutics-Treated Acute Lymphoblastic Leukemia Cells by Time-Lapse ImagingHsiao-Chuan Liu0Eun Ji Gang1Hye Na Kim2Yongsheng Ruan3Heather Ogana4Zesheng Wan5Halvard Bönig6K. Kirk Shung7Yong-Mi Kim8Department of Radiology, Mayo Clinic, Rochester, MN 55905, USADepartment of Pediatrics, Division of Hematology, Oncology, Blood and Marrow Transplantation, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, CA 90027, USADepartment of Pediatrics, Division of Hematology, Oncology, Blood and Marrow Transplantation, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, CA 90027, USADepartment of Pediatrics, Division of Hematology, Oncology, Blood and Marrow Transplantation, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, CA 90027, USADepartment of Pediatrics, Division of Hematology, Oncology, Blood and Marrow Transplantation, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, CA 90027, USADepartment of Pediatrics, Division of Hematology, Oncology, Blood and Marrow Transplantation, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, CA 90027, USAGoethe University School of Medicine, Institute for Transfusion Medicine and Immunohematology and German Red Cross Blood Service BaWuHe, 60528 Frankfurt, GermanyDepartment of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USADepartment of Pediatrics, Division of Hematology, Oncology, Blood and Marrow Transplantation, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, CA 90027, USADrug resistance is an obstacle in the therapy of acute lymphoblastic leukemia (ALL). Whether the physical properties such as the motility of the cells contribute to the survival of ALL cells after drug treatment has recently been of increasing interest, as they could potentially allow the metastasis of solid tumor cells and the migration of leukemia cells. We hypothesized that chemotherapeutic treatment may alter these physical cellular properties. To investigate the motility of chemotherapeutics-treated B-cell ALL (B-ALL) cells, patient-derived B-ALL cells were treated with chemotherapy for 7 days and left for 12 h without chemotherapeutic treatment. Two parameters of motility were studied, velocity and migration distance, using a time-lapse imaging system. The study revealed that compared to non-chemotherapeutically treated B-ALL cells, B-ALL cells that survived chemotherapy treatment after 7 days showed reduced motility. We had previously shown that Tysabri and P5G10, antibodies against the adhesion molecules integrins α4 and α6, respectively, may overcome drug resistance mediated through leukemia cell adhesion to bone marrow stromal cells. Therefore, we tested the effect of integrin α4 or α6 blockade on the motility of chemotherapeutics-treated ALL cells. Only integrin α4 blockade decreased the motility and velocity of two chemotherapeutics-treated ALL cell lines. Interestingly, integrin α6 blockade did not affect the velocity of chemoresistant ALL cells. This study explores the physical properties of the movements of chemoresistant B-ALL cells and highlights a potential link to integrins. Further studies to investigate the underlying mechanism are warranted.https://www.mdpi.com/2073-4409/9/6/1470acute lymphoblastic leukemiachemotherapeutics-treatedtime-lapse imagingcell motilityintegrins |
| spellingShingle | Hsiao-Chuan Liu Eun Ji Gang Hye Na Kim Yongsheng Ruan Heather Ogana Zesheng Wan Halvard Bönig K. Kirk Shung Yong-Mi Kim Characterizing the Motility of Chemotherapeutics-Treated Acute Lymphoblastic Leukemia Cells by Time-Lapse Imaging Cells acute lymphoblastic leukemia chemotherapeutics-treated time-lapse imaging cell motility integrins |
| title | Characterizing the Motility of Chemotherapeutics-Treated Acute Lymphoblastic Leukemia Cells by Time-Lapse Imaging |
| title_full | Characterizing the Motility of Chemotherapeutics-Treated Acute Lymphoblastic Leukemia Cells by Time-Lapse Imaging |
| title_fullStr | Characterizing the Motility of Chemotherapeutics-Treated Acute Lymphoblastic Leukemia Cells by Time-Lapse Imaging |
| title_full_unstemmed | Characterizing the Motility of Chemotherapeutics-Treated Acute Lymphoblastic Leukemia Cells by Time-Lapse Imaging |
| title_short | Characterizing the Motility of Chemotherapeutics-Treated Acute Lymphoblastic Leukemia Cells by Time-Lapse Imaging |
| title_sort | characterizing the motility of chemotherapeutics treated acute lymphoblastic leukemia cells by time lapse imaging |
| topic | acute lymphoblastic leukemia chemotherapeutics-treated time-lapse imaging cell motility integrins |
| url | https://www.mdpi.com/2073-4409/9/6/1470 |
| work_keys_str_mv | AT hsiaochuanliu characterizingthemotilityofchemotherapeuticstreatedacutelymphoblasticleukemiacellsbytimelapseimaging AT eunjigang characterizingthemotilityofchemotherapeuticstreatedacutelymphoblasticleukemiacellsbytimelapseimaging AT hyenakim characterizingthemotilityofchemotherapeuticstreatedacutelymphoblasticleukemiacellsbytimelapseimaging AT yongshengruan characterizingthemotilityofchemotherapeuticstreatedacutelymphoblasticleukemiacellsbytimelapseimaging AT heatherogana characterizingthemotilityofchemotherapeuticstreatedacutelymphoblasticleukemiacellsbytimelapseimaging AT zeshengwan characterizingthemotilityofchemotherapeuticstreatedacutelymphoblasticleukemiacellsbytimelapseimaging AT halvardbonig characterizingthemotilityofchemotherapeuticstreatedacutelymphoblasticleukemiacellsbytimelapseimaging AT kkirkshung characterizingthemotilityofchemotherapeuticstreatedacutelymphoblasticleukemiacellsbytimelapseimaging AT yongmikim characterizingthemotilityofchemotherapeuticstreatedacutelymphoblasticleukemiacellsbytimelapseimaging |