TY - JOUR
T1 - Fibronectin regulation of integrin b1 and slug in circulating tumor cells
AU - Huaman, Jeannette
AU - Naidoo, Michelle
AU - Zang, Xingxing
AU - Ogunwobi, Olorunseun O.
N1 - Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - Castration resistant prostate cancer (CRPC)
KW - Circulating tumor cells (CTCs)
KW - Epithelial-to-mesenchymal transition (EMT)
KW - Fibronectin
KW - Hepatocellular carcinoma (HCC)
KW - Immunomodulation
KW - Integrin B1
KW - Major histocompatibility complex class I (MHCI)
KW - Metastasis
KW - SLUG
UR - http://www.scopus.com/inward/record.url?scp=85086044588&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85086044588&partnerID=8YFLogxK
U2 - 10.3390/cells8060618
DO - 10.3390/cells8060618
M3 - Article
AN - SCOPUS:85086044588
SN - 2073-4409
VL - 8
JO - Cells
JF - Cells
IS - 6
M1 - 618
ER -