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 o… Show more
“…Boelens and colleagues demonstrated in an in vitro and in vivo model of breast cancer that fibroblast derived exosomes induce a CSC like phenotype in breast cancer cells by Neurogenic locus notch homolog protein 3 (Notch3)/ Signal transducer and activator of transcription 1 (STAT1) signalling which is associated with radiochemotherapy resistance [73]. Exosomal IL-6, Activin-A and granulocyte colony stimulating factor (G-CSF) induced de-differentiation of lung carcinoma cells to a more CSC-like phenotype and reduced cell cycle progression, which was associated with higher methotrexate resistance [74]. Besides promoting CSC-like phenotypes and dormancy in cancer cells, exosomes from fibroblasts can reverse this dormant phenotype by transferring mitochondrial DNA and inducing oxidative phosphorylation allowing recurrence of the disease and metastasis [75].…”
Therapy resistance can arise within tumor cells because of genetic or phenotypic changes (intrinsic resistance), or it can be the result of an interaction with the tumor microenvironment (extrinsic resistance). Exosomes are membranous vesicles 40 to 100 nm in diameter constitutively released by almost all cell types, and mediate cell-to-cell communication by transferring mRNAs, miRNAs, DNAs and proteins causing extrinsic therapy resistance. They transfer therapy resistance by anti-apoptotic signalling, increased DNA-repair or delivering ABC transporters to drug sensitive cells. As functional mediators of tumor-stroma interaction and of epithelial to mesenchymal transition, exosomes also promote environment-mediated therapy resistance.
Exosomes may be used in anticancer therapy exploiting their delivery function. They may effectively transfer anticancer drugs or RNAs in the context of gene therapy reducing immune stimulatory effects of these drugs and hydrophilic qualities facilitating crossing of cell membranes.
“…Boelens and colleagues demonstrated in an in vitro and in vivo model of breast cancer that fibroblast derived exosomes induce a CSC like phenotype in breast cancer cells by Neurogenic locus notch homolog protein 3 (Notch3)/ Signal transducer and activator of transcription 1 (STAT1) signalling which is associated with radiochemotherapy resistance [73]. Exosomal IL-6, Activin-A and granulocyte colony stimulating factor (G-CSF) induced de-differentiation of lung carcinoma cells to a more CSC-like phenotype and reduced cell cycle progression, which was associated with higher methotrexate resistance [74]. Besides promoting CSC-like phenotypes and dormancy in cancer cells, exosomes from fibroblasts can reverse this dormant phenotype by transferring mitochondrial DNA and inducing oxidative phosphorylation allowing recurrence of the disease and metastasis [75].…”
Therapy resistance can arise within tumor cells because of genetic or phenotypic changes (intrinsic resistance), or it can be the result of an interaction with the tumor microenvironment (extrinsic resistance). Exosomes are membranous vesicles 40 to 100 nm in diameter constitutively released by almost all cell types, and mediate cell-to-cell communication by transferring mRNAs, miRNAs, DNAs and proteins causing extrinsic therapy resistance. They transfer therapy resistance by anti-apoptotic signalling, increased DNA-repair or delivering ABC transporters to drug sensitive cells. As functional mediators of tumor-stroma interaction and of epithelial to mesenchymal transition, exosomes also promote environment-mediated therapy resistance.
Exosomes may be used in anticancer therapy exploiting their delivery function. They may effectively transfer anticancer drugs or RNAs in the context of gene therapy reducing immune stimulatory effects of these drugs and hydrophilic qualities facilitating crossing of cell membranes.
“…For example, PC-derived exosomes (isolated from murine pancreatic cancer cells) could inhibit glucose intake and promote lipidosis, developing an eventual state of insulin resistance in skeletal muscle cells [142]. The newest documents have found that the exosomes can induce the formation of cancer stem cells (CSCs) to decrease the effect of chemo- and radio-therapy [145–147] ( Fig. 4 ) .Fig.…”
Reprogramming of cancer metabolism is a newly recognized hallmark of malignancy. The aberrant glucose metabolism is associated with dramatically increased bioenergetics, biosynthetic, and redox demands, which is vital to maintain rapid cell proliferation, tumor progression, and resistance to chemotherapy and radiation. When the glucose metabolism of cancer is rewiring, the characters of cancer will also occur corresponding changes to regulate the chemo- and radio-resistance of cancer. The procedure is involved in the alteration of many activities, such as the aberrant DNA repairing, enhanced autophagy, oxygen-deficient environment, and increasing exosomes secretions, etc. Targeting altered metabolic pathways related with the glucose metabolism has become a promising anti-cancer strategy. This review summarizes recent progress in our understanding of glucose metabolism in chemo- and radio-resistance malignancy, and highlights potential molecular targets and their inhibitors for cancer treatment.
“…Activin A was described to maintain pluripotency of human embryonic stem cells (hESC) [70] and was also used in protocols to differentiate them into, for instance, insulin-producing cells [71] and hepatocytes [72]. With respect to cancer stem cells -a controversial field in many cancer types -activin A was postulated to drive self-renewal of pancreatic [73] and colorectal [74] cancer stem cells and support cancer stem celllike features in lung cancer [75,76] and mesothelioma cells [77]. One characteristic feature of stem cells is their high degree of drug resistance.…”
Section: Activin a In Stemness And Drug Resistancementioning
Introduction: Activin A is involved in the regulation of a surprisingly broad number of processes that are relevant for cancer development and treatment; it is implicated in cell autonomous functions and multiple regulatory functions in the tumor microenvironment. Areas covered: This article summarizes the current knowledge about activin A in cell growth and death, migration and metastasis, angiogenesis, stemness and drug resistance, regulation of antitumor immunity, and cancer cachexia. We explore the role of activin A as a biomarker and discuss strategies for using it as target for cancer therapy. Literature retrieved from Medline until 25 June 2020 was considered. Expert opinion: While many functions of activin A were investigated in preclinical models, there is currently limited experience from clinical trials. Activin A has growth-and migration-promoting effects, contributes to immune evasion and cachexia and is associated with shorter survival in several cancer types. Targeting activin A could offer the chance to simultaneously limit tumor growth and spreading, improve drug response, boost antitumor immune responses and improve cancer-associated or treatment-associated cachexia, bone loss, and anemia. Nevertheless, defining which patients have the highest likelihood of benefiting from these effects is challenging and will require further work.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
