Glioblastoma cancer stem cells: heterogeneity, microenvironment and related therapeutic strategies.
Glioblastoma Multiforme (GBM) is an incurable malignancy. GBM patients have a short life expectancy despite aggressive therapeutic approaches based on surgical resection followed by adjuvant radiotherapy and concomitant chemotherapy. Glioblastoma growth is characterized by a high motility of tumour cells, their resistance to both chemo/radio-therapy, apoptosis inhibition leading to failure of conventional therapy. Cancer Stem Cells (CSCs), identified in GBM as well as in many other cancer types, express the membrane antigen prominin-1 (namely CD133). These cells and normal Neural Stem Cells (NSC) share surface markers and properties, i.e. are able to self-renew and differentiate into multiple cell types. Stem cell self-renewal depends on microenvironmental cues, including Extracellular Matrix (ECM) composition and cell types. Therefore, the role of microenvironment needs to be evaluated to clarify its importance in tumour initiation and progression through CSCs. The specific microenvironment of CSCs was found to mimic in part the vascular niche of normal stem cells. The targeting of GMB CSCs may represent a powerful treatment approach. Lastly, in GBM patients cancer-initiating cells contribute to the profound immune suppression that in turn correlated with CSCs STAT3 (CD133 + ). Further studies of microenvironment are needed to better understand the origin of GMB/GBM CSCs and its immunosuppressive properties.
Denysenko
Tetyana
T
CeRMS, Center for Experimental Research and Medical Studies, Turin, Italy. de_tanya@yahoo.com
Gennero
Luisa
L
Roos
Maria Augusta
MA
Melcarne
Antonio
A
Juenemann
Carola
C
Faccani
Giuliano
G
Morra
Isabella
I
Cavallo
Giovanni
G
Reguzzi
Stefano
S
Pescarmona
Gianpiero
G
Ponzetto
Antonio
A
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D005909:Glioblastoma / Q000276:immunology / Q000628:therapy*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides