Breast cancer stem cells, cytokine networks, and the tumor microenvironment

Abstract

Many tumors, including breast cancer, are maintained by a subpopulation of cells that display stem cell properties, mediate metastasis, and contribute to treatment resistance. These cancer stem cells (CSCs) are regulated by complex interactions with the components of the tumor microenvironment -including mesenchymal stem cells, adipocytes, tumor associated fibroblasts, endothelial cells, and immune cells -through networks of cytokines and growth factors. Since these components have a direct influence on CSC properties, they represent attractive targets for therapeutic development.

Laparoscopic surgery for colorectal cancer is not associated with an increase in the circulating levels of several inflammation-related factors

“…[12][13][14][15] Moreover, inflammatory cytokines can play a pivotal role being able to exert pleiotropic effects both directly on tumor cells (i.e., EMT induction and CSCs activation) and indirectly by promoting favorable conditions within the microenvironment (including the suppression of the antitumor activity of immune cells). 2,4,7,12,13,[16][17][18] Since surgery, chemotherapy and radiation therapies, by damaging both normal and cancer tissues, trigger a strong inflammatory response, it has been hypothesized that they might induce the release of molecules that could facilitate both EMT induction and stem cell activation and ultimately promote proliferation, invasion and metastasis of surviving cancer cells. 19 Inflammatory cytokines are grouped into 9 categories: chemokines, interferons (IFNs), tumor necrosis factors (TNFs), transforming growth factor-b (TGF-b) family members, interleukin-1 (IL-1) family members (such as IL-1a, IL-1b, and IL-18), IL-10 family members, IL-17 family members, haematopoietic growth factors (such as IL-1, G-CSF, GM-CSF), and platelet derived growth factors (PDGFs).…”

Nuclear receptors agonists exert opposing effects on the inflammation dependent survival of breast cancer stem cells

“…2,3 CSCs are likely to sustain the growth of the primary tumor mass, as well as to be responsible for disease relapse and metastatic spreading. 4,5 Consequently, CSCs represent the most significant target for new anti-cancer drugs. 3 Cells disclosing a CSCs phenotype can be expanded in vitro as multicellular spheroids, named mammospheres (MS), obtained from breast cancer surgical specimens and cell lines.…”

Cancer Stem Cells: Formidable Allies of Cancer

“…Tumour cells can cause epigenetic changes in the non-tumorigenic cells of the tumour microenvironment, which in turn, releases factors that cause epigenetic changes in the tumour cells [83,84]. Cytokines (specifically IL-6 and IL-8), TGFβ, IGF, PDGF, Wnt, Hedgehog ligands, Notch ligands, and MMPs are some factors released by the cells in the TME that regulate tumour progression, invasion and metastasis [85][86][87].…”