Coculture with Neural Stem Cells May Shift the Transcription Profile of Glioblastoma Multiforme towards Cancer-Specific Stemness

• Published in: International journal of molecular sciences Vol. 24; no. 4; p. 3242
• Main Authors: Vaidya, Manjusha, Sreerama, Sandeep, Gonzalez-Vega, Maxine, Smith, Jonhoi, Field, Melvin, Sugaya, Kiminobu
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.02.2023; MDPI
• Subjects: ABC transporter gene; ABC transporters; Brain cancer; Brain Neoplasms - metabolism; Cancer; cancer stem cells; Cancer therapies; Carcinogenesis - metabolism; Cell differentiation; Cell Differentiation - genetics; Cell Line, Tumor; Cell self-renewal; Chemokines; Chemotherapy; Coculture Techniques; Communication; Cytokines; DNA repair; Drug resistance; Efflux; Extracellular vesicles; Gene expression; Gene regulation; Genes; Genetic aspects; Genetic transcription; Glioblastoma; Glioblastoma - metabolism; Glioblastoma multiforme; Growth factors; Humans; Invasiveness; Metastases; Mutation; Neoplastic Stem Cells - metabolism; Neural stem cells; Neural Stem Cells - metabolism; Permeability; Pore size; Propagation; Proteins; Radiotherapy; Stem cells; stemness genes; Transcription; Tumorigenesis; glioblastoma multiforme; stemness genes; extracellular vesicles; cancer stem cells; ABC transporter gene; neural stem cells
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24043242

Glioblastoma multiforme (GBM) possesses a small but significant population of cancer stem cells (CSCs) thought to play a role in its invasiveness, recurrence, and metastasis. The CSCs display transcriptional profiles for multipotency, self-renewal, tumorigenesis, and therapy resistance. There are two possible theories regarding the origin of CSCs in the context of neural stem cells (NSCs); i.e., NSCs modify cancer cells by conferring them with cancer-specific stemness, or NSCs themselves are transformed into CSCs due to the tumor environment created by cancer cells. To test the theories and to investigate the transcriptional regulation of the genes involved in CSC formation, we cocultured NSC and GBM cell lines together. Where genes related to cancer stemness, drug efflux, and DNA modification were upregulated in GBM, they were downregulated in NSCs upon coculture. These results indicate that cancer cells shift the transcriptional profile towards stemness and drug resistance in the presence of NSCs. Concurrently, GBM triggers NSCs differentiation. Because the cell lines were separated by a membrane (0.4 µm pore size) to prevent direct contact between GBM and NSCs, cell-secreted signaling molecules and extracellular vesicles (EVs) are likely involved in reciprocal communication between NSCs and GBM, causing transcription modification. Understanding the mechanism of CSC creation will aid in the identification of precise molecular targets within the CSCs to exterminate them, which, in turn, will increase the efficacy of chemo-radiation treatment.