Fibronectin Regulation of Integrin B1 and SLUG in Circulating Tumor Cells
Metastasis is the leading cause of cancer death worldwide. Circulating tumor cells (CTCs) are a critical step in the metastatic cascade and a good tool to study this process. We isolated CTCs from a syngeneic mouse model of hepatocellular carcinoma (HCC) and a human xenograft mouse model of castrati...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-06-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/8/6/618 |
| _version_ | 1797709230352891904 |
|---|---|
| author | Jeannette Huaman Michelle Naidoo Xingxing Zang Olorunseun O. Ogunwobi |
| author_facet | Jeannette Huaman Michelle Naidoo Xingxing Zang Olorunseun O. Ogunwobi |
| author_sort | Jeannette Huaman |
| collection | DOAJ |
| description | Metastasis is the leading cause of cancer death worldwide. Circulating tumor cells (CTCs) are a critical step in the metastatic cascade and a good tool to study this process. We isolated CTCs from a syngeneic mouse model of hepatocellular carcinoma (HCC) and a human xenograft mouse model of castration-resistant prostate cancer (CRPC). From these models, novel primary tumor and CTC cell lines were established. CTCs exhibited greater migration than primary tumor-derived cells, as well as epithelial-to-mesenchymal transition (EMT), as observed from decreased E-cadherin and increased SLUG and fibronectin expression. Additionally, when fibronectin was knocked down in CTCs, integrin B1 and SLUG were decreased, indicating regulation of these molecules by fibronectin. Investigation of cell surface molecules and secreted cytokines conferring immunomodulatory advantage to CTCs revealed decreased major histocompatibility complex class I (MHCI) expression and decreased endostatin, C-X-C motif chemokine 5 (CXCL5), and proliferin secretion by CTCs. Taken together, these findings indicate that CTCs exhibit distinct characteristics from primary tumor-derived cells. Furthermore, CTCs demonstrate enhanced migration in part through fibronectin regulation of integrin B1 and SLUG. Further study of CTC biology will likely uncover additional important mechanisms of cancer metastasis. |
| first_indexed | 2024-03-12T06:34:30Z |
| format | Article |
| id | doaj.art-ccd07530c1c849bd92e3ce1f22657345 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T06:34:30Z |
| publishDate | 2019-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-ccd07530c1c849bd92e3ce1f226573452023-09-03T01:27:59ZengMDPI AGCells2073-44092019-06-018661810.3390/cells8060618cells8060618Fibronectin Regulation of Integrin B1 and SLUG in Circulating Tumor CellsJeannette Huaman0Michelle Naidoo1Xingxing Zang2Olorunseun O. Ogunwobi3Department of Biological Sciences, Hunter College of The City University of New York, New York, NY 10065, USADepartment of Biological Sciences, Hunter College of The City University of New York, New York, NY 10065, USADepartments of Microbiology and Immunology, and Medicine (Oncology), Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Biological Sciences, Hunter College of The City University of New York, New York, NY 10065, USAMetastasis is the leading cause of cancer death worldwide. Circulating tumor cells (CTCs) are a critical step in the metastatic cascade and a good tool to study this process. We isolated CTCs from a syngeneic mouse model of hepatocellular carcinoma (HCC) and a human xenograft mouse model of castration-resistant prostate cancer (CRPC). From these models, novel primary tumor and CTC cell lines were established. CTCs exhibited greater migration than primary tumor-derived cells, as well as epithelial-to-mesenchymal transition (EMT), as observed from decreased E-cadherin and increased SLUG and fibronectin expression. Additionally, when fibronectin was knocked down in CTCs, integrin B1 and SLUG were decreased, indicating regulation of these molecules by fibronectin. Investigation of cell surface molecules and secreted cytokines conferring immunomodulatory advantage to CTCs revealed decreased major histocompatibility complex class I (MHCI) expression and decreased endostatin, C-X-C motif chemokine 5 (CXCL5), and proliferin secretion by CTCs. Taken together, these findings indicate that CTCs exhibit distinct characteristics from primary tumor-derived cells. Furthermore, CTCs demonstrate enhanced migration in part through fibronectin regulation of integrin B1 and SLUG. Further study of CTC biology will likely uncover additional important mechanisms of cancer metastasis.https://www.mdpi.com/2073-4409/8/6/618metastasiscirculating tumor cells (CTCs)hepatocellular carcinoma (HCC)castration resistant prostate cancer (CRPC)epithelial-to-mesenchymal transition (EMT)fibronectinintegrin B1SLUGmajor histocompatibility complex class I (MHCI)immunomodulation |
| spellingShingle | Jeannette Huaman Michelle Naidoo Xingxing Zang Olorunseun O. Ogunwobi Fibronectin Regulation of Integrin B1 and SLUG in Circulating Tumor Cells Cells metastasis circulating tumor cells (CTCs) hepatocellular carcinoma (HCC) castration resistant prostate cancer (CRPC) epithelial-to-mesenchymal transition (EMT) fibronectin integrin B1 SLUG major histocompatibility complex class I (MHCI) immunomodulation |
| title | Fibronectin Regulation of Integrin B1 and SLUG in Circulating Tumor Cells |
| title_full | Fibronectin Regulation of Integrin B1 and SLUG in Circulating Tumor Cells |
| title_fullStr | Fibronectin Regulation of Integrin B1 and SLUG in Circulating Tumor Cells |
| title_full_unstemmed | Fibronectin Regulation of Integrin B1 and SLUG in Circulating Tumor Cells |
| title_short | Fibronectin Regulation of Integrin B1 and SLUG in Circulating Tumor Cells |
| title_sort | fibronectin regulation of integrin b1 and slug in circulating tumor cells |
| topic | metastasis circulating tumor cells (CTCs) hepatocellular carcinoma (HCC) castration resistant prostate cancer (CRPC) epithelial-to-mesenchymal transition (EMT) fibronectin integrin B1 SLUG major histocompatibility complex class I (MHCI) immunomodulation |
| url | https://www.mdpi.com/2073-4409/8/6/618 |
| work_keys_str_mv | AT jeannettehuaman fibronectinregulationofintegrinb1andslugincirculatingtumorcells AT michellenaidoo fibronectinregulationofintegrinb1andslugincirculatingtumorcells AT xingxingzang fibronectinregulationofintegrinb1andslugincirculatingtumorcells AT olorunseunoogunwobi fibronectinregulationofintegrinb1andslugincirculatingtumorcells |