Abstract
Cancer stem cells (CSCs) are a small population of resistant cells inhabiting the tumors. Although comprising only nearly 3% of the tumor mass, these cells were demonstrated to orchestrate tumorigenesis and differentiation, underlie tumors’ heterogeneity and mediate therapy resistance and tumor relapse. Here we show that CSCs may be formed by dedifferentiation of terminally differentiated tumor cells under stress conditions. Using a elegant co-culture cellular system, we were able to prove that nutrients and oxygen deprivation activated non-malignant stromal fibroblasts, which in turn established with tumor cells a paracrine loop mediated by Interleukine-6 (IL-6), Activin-A and Granulocyte colony-stimulating factor (G-CSF), that drove subsequent tumor formation and cellular dedifferentiation. However, by scavenging these cytokines from the media and/or blocking exosomes’ mediated communication it was possible to abrogate dedifferentiation thus turning these mechanisms into potential therapeutic targets against cancer progression.
Highlights
Tumors are dynamic and heterogeneous entities that act like organs in a perfect trading with the entire body
Exploiting the recently evoked involvement of microenvironment and cytokines and soluble molecules in keeping and inducing Cancer stem cells (CSCs)’ phenotype may constitute a new molecule-focused therapeutic opportunity. In this line, using an elegant cell culture model previously developed in the laboratory we were able to show that IL-6, Granulocyte colony-stimulating factor (G-CSF) and Activin-A released by stromal fibroblasts drive lung carcinoma cells’ dedifferentiation and CSCs formation
This chemical agent was classified by both the IACR and the United States Environmental Protection Agency (USEPA) as a human lung carcinogen of Group I and Group A, respectively[10], and its concentration was selected based on epidemiologic studies[11,12] and the observation that it was only slightly cytotoxic[13]
Summary
Tumors are dynamic and heterogeneous entities that act like organs in a perfect trading with the entire body. CSCs share several similarities with normal adult stem cells (SCs), including self-renewal capacity, expression of pluripotency surface markers and multilineage differentiation properties[2], but unlike them, CSCs have sustained cellular proliferation[3] Their tremendously variable frequency among the different tumor types, and within tumors of the same origin, makes them difficult to ascertain[4]. Exploiting the recently evoked involvement of microenvironment and cytokines and soluble molecules in keeping and inducing CSCs’ phenotype may constitute a new molecule-focused therapeutic opportunity In this line, using an elegant cell culture model previously developed in the laboratory we were able to show that IL-6, G-CSF and Activin-A released by stromal fibroblasts drive lung carcinoma cells’ dedifferentiation and CSCs formation. The attained results sustain the active role of microenvironment in tumor progression and present a new avenue for therapeutic intervention aiming CSCs ablation and metastasis abrogation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
