Invasive Glioblastoma Cells Acquire Stemness and Increased Akt Activation
Glioblastoma multiforme (GBM) is the most frequent and most aggressive brain tumor in adults. The dismal prognosis is due to postsurgery recurrences arising from escaped invasive tumor cells. The signaling pathways activated in invasive cells are under investigation, and models are currently designe...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2010-06-01
|
| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S147655861080003X |
| _version_ | 1811245411772399616 |
|---|---|
| author | Jennifer R. Molina Yuho Hayashi Clifton Stephens Maria-Magdalena Georgescu |
| author_facet | Jennifer R. Molina Yuho Hayashi Clifton Stephens Maria-Magdalena Georgescu |
| author_sort | Jennifer R. Molina |
| collection | DOAJ |
| description | Glioblastoma multiforme (GBM) is the most frequent and most aggressive brain tumor in adults. The dismal prognosis is due to postsurgery recurrences arising from escaped invasive tumor cells. The signaling pathways activated in invasive cells are under investigation, and models are currently designed in search for therapeutic targets. We developed here an in vivo model of human invasive GBM in mouse brain from a GBM cell line with moderate tumorigenicity that allowed simultaneous primary tumor growth and dispersal of tumor cells in the brain parenchyma. This strategy allowed for the first time the isolation and characterization of matched sets of tumor mass (Core) and invasive (Inv) cells. Both cell populations, but more markedly Inv cells, acquired stem cell markers, neurosphere renewal ability, and resistance to rapamycin-induced apoptosis relative to parental cells. The comparative phenotypic analysis between Inv and Core cells showed significantly increased tumorigenicity in vivo and increased invasion with decreased proliferation in vitro for Inv cells. Examination of a large array of signaling pathways revealed extracellular signal-regulated kinase (Erk) down-modulation and Akt activation in Inv cells and an opposite profile in Core cells. Akt activation correlated with the increased tumorigenicity, stemness, and invasiveness, whereas Erk activation correlated with the proliferation of the cells. These results underscore complementary roles of the Erk and Akt pathways for GBM proliferation and dispersal and raise important implications for a concurrent inhibitory therapy. |
| first_indexed | 2024-04-12T14:39:42Z |
| format | Article |
| id | doaj.art-2f5f88b5c51343fab3ad6ac05b51d4dc |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-04-12T14:39:42Z |
| publishDate | 2010-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-2f5f88b5c51343fab3ad6ac05b51d4dc2022-12-22T03:28:55ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022010-06-0112645346310.1593/neo.10126Invasive Glioblastoma Cells Acquire Stemness and Increased Akt ActivationJennifer R. Molina0Yuho Hayashi1Clifton Stephens2Maria-Magdalena Georgescu3Department of Neuro-oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Neuro-oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Neuro-oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USAGlioblastoma multiforme (GBM) is the most frequent and most aggressive brain tumor in adults. The dismal prognosis is due to postsurgery recurrences arising from escaped invasive tumor cells. The signaling pathways activated in invasive cells are under investigation, and models are currently designed in search for therapeutic targets. We developed here an in vivo model of human invasive GBM in mouse brain from a GBM cell line with moderate tumorigenicity that allowed simultaneous primary tumor growth and dispersal of tumor cells in the brain parenchyma. This strategy allowed for the first time the isolation and characterization of matched sets of tumor mass (Core) and invasive (Inv) cells. Both cell populations, but more markedly Inv cells, acquired stem cell markers, neurosphere renewal ability, and resistance to rapamycin-induced apoptosis relative to parental cells. The comparative phenotypic analysis between Inv and Core cells showed significantly increased tumorigenicity in vivo and increased invasion with decreased proliferation in vitro for Inv cells. Examination of a large array of signaling pathways revealed extracellular signal-regulated kinase (Erk) down-modulation and Akt activation in Inv cells and an opposite profile in Core cells. Akt activation correlated with the increased tumorigenicity, stemness, and invasiveness, whereas Erk activation correlated with the proliferation of the cells. These results underscore complementary roles of the Erk and Akt pathways for GBM proliferation and dispersal and raise important implications for a concurrent inhibitory therapy.http://www.sciencedirect.com/science/article/pii/S147655861080003X |
| spellingShingle | Jennifer R. Molina Yuho Hayashi Clifton Stephens Maria-Magdalena Georgescu Invasive Glioblastoma Cells Acquire Stemness and Increased Akt Activation Neoplasia: An International Journal for Oncology Research |
| title | Invasive Glioblastoma Cells Acquire Stemness and Increased Akt Activation |
| title_full | Invasive Glioblastoma Cells Acquire Stemness and Increased Akt Activation |
| title_fullStr | Invasive Glioblastoma Cells Acquire Stemness and Increased Akt Activation |
| title_full_unstemmed | Invasive Glioblastoma Cells Acquire Stemness and Increased Akt Activation |
| title_short | Invasive Glioblastoma Cells Acquire Stemness and Increased Akt Activation |
| title_sort | invasive glioblastoma cells acquire stemness and increased akt activation |
| url | http://www.sciencedirect.com/science/article/pii/S147655861080003X |
| work_keys_str_mv | AT jenniferrmolina invasiveglioblastomacellsacquirestemnessandincreasedaktactivation AT yuhohayashi invasiveglioblastomacellsacquirestemnessandincreasedaktactivation AT cliftonstephens invasiveglioblastomacellsacquirestemnessandincreasedaktactivation AT mariamagdalenageorgescu invasiveglioblastomacellsacquirestemnessandincreasedaktactivation |