hyaluronic_acid   13

Proinvasive extracellular matrix remodeling in tumor microenvironment in response to radiation | Oncogene
I wonder if macrophages could provide the IL1A to trigger HA to stimulate CD44...

Ionizing radiation is widely used for patient with glioblastoma (GBM). However, the effect of radiation on patient survival is marginal and upon recurrence tumors frequently shift toward mesenchymal subtype adopting invasiveness. Here, we show that ionizing radiation affects biomechanical tension in GBM microenvironment and provides proinvasive extracellular signaling cue, hyaluronic acid (HA)-rich condition. In response to radiation, HA production was increased in GBM cells by HA synthase-2 (HAS2) that was transcriptionally upregulated by NF-ĸB. Notably, NF-ĸB was persistently activated by IL-1α-feedback loop, making HA abundance in tumor microenvironment after radiation. Radiation-induced HA abundance causally has been linked to invasiveness of GBM cells by generating movement track as an extracellular matrix, and by acting as a signaling ligand for CD44 receptor, leading to SRC activation, which is sufficient for mesenchymal shift of GBM cells. Collectively, our findings provide an explanation for the frequent brain tumor relapse after radiotherapy, and potential therapeutic targets to block mesenchymal shift upon relapse.
radiation  il1alpha  nfkb  hyaluronic_acid  U87 
february 2019 by Segalllab
Activation of the FGFR–STAT3 Pathway in Breast Cancer Cells Induces a Hyaluronan-Rich Microenvironment That Licenses Tumor Formation
a stat3 target is HAS2, which can increase hyaluronan production and this could stimulate migration through growth factor binding to ECM. They find stat3 ser phospohrylation is rapid after FGFR stimulation but tyr is slow (2 hours) and they propose that it is through production of IL6 which then phosphorylates STAT3 tyr. However, this was more stat3tyr regulated perhaps, and they discuss FGFR activation, not EGFR - perhaps EGFR would work similarly in HNSCC?
stat3  hyaluronic_acid  fgfr  il6 
march 2014 by Segalllab
Regulation of glioma cell phenotype in 3D matrices by hyaluronic acid
looked at U87 cells parental or +EGFR in hydrogels with increased HA - see increased invasiveness in cells expressing increased EGFR.
EGFR  spheroid  CD44  hyaluronic_acid  U87 
october 2013 by Segalllab
Hyaluronan Facilitates Transforming Growth Factor-β1-dependent Proliferation via CD44 and Epidermal Growth Factor Receptor Interaction
very complicated, but basically increased levels of HA lead to clustering of EGFR and CD44 (HA receptor) which then seem to be able to mediate ERK activation by TGFB.
egfr  cd44  hyaluronic_acid 
july 2011 by Segalllab
Hyaluronan Deficiency in Tumor Stroma Impairs Macrophage Trafficking and Tumor Neovascularization — Cancer Res
tumor fibroblasts make HA which in turn then enhances TAM association with tumors, stimulating (at least) vascularization (possibly invasion?). There may be something iffy about the model (only tested in their tumor which is not clearly described here) but still worth keeping in mind
hyaluronic_acid  breast_cancer  TAMs 
october 2010 by Segalllab
Aging Fibroblasts Resist Phenotypic Maturation Because of Impaired Hyaluronan-Dependent CD44/Epidermal Growth Factor Receptor Signaling -- Simpson et al. 176 (3): 1215 Figure 11 -- American Journal of Pathology
An interesting combination of TGFbeta, EGFR, HA and CD44: they hypothesize that TGFbeta can stimulate EGFR ligand release, stimulating EGFR to activate HA synthetase, producing HA which can bind CD44 and stimulate complex formation with EGFR. This is for generation of activated fibroblasts, and this could apply either to activation of fibroblasts in the primary tumor microenvironment or possibly activation of tumor cells. Tumor cells secreting EGF and TGFbeta could generate activated fibroblasts, which in turn activate the tumor cells...
EGFR  tgfbeta  ligands  cd44  hyaluronic_acid  fibroblasts  zhenni 
march 2010 by Segalllab

related tags

231_cells  alpha5_integrin  beta1_integrin  breast_cancer  cd44  cxcr4  dmitriy  egfr  elisa  erbb2  extravasation  fgfr  fibroblasts  fibronectin  general  glioma  il1alpha  il6  intravasation  ligands  nfkb  paxillin  radiation  sdf_1  spheroid  stat3  talin  tams  tgfbeta  trastuzumab  u87  zhenni 

Copy this bookmark: