Elevated CAF levels in a large subpopulation of sarcopenic patients suggest the existence of a specific form of sarcopenia for which CAF could become a biomarker and a new target for therapeutic interventions.
Changes in CAF levels between T0 (baseline) and T1 (after 4 weeks of treatment) were tested by means of paired Student's t-tests.
We examined the effect of CAF on level of phosphorylated Akt in 3T3-L1 cells treated with CAF at various concentrations during adipocyte differentiation.
To explore a potential role for IGF II in the growth modulation of breast epithelial cells by NAF and CAF, the level of expression of IGF II in CAF versus that in NAF was assessed.
Concerning soluble factors secreted from CAFs, the level of SDF-1 in tumor tissues was significantly decreased, associated with reduction of CAFs (anti-CAFs vs vehicle, P = 0.007) (Figs 1b, S2).
Intriguingly, when mesenchymal stem cells (MSCs) were induced to form CAFs, Int6 levels were reduced.
Clearly different response was seen with CAF-43 cells where, instead of downregulation of FSP1, the levels increased in nemosis.The heterogeneity of fibroblasts becomes evident when looking at the basal levels of the CAF marker expression; CAF-43 cells had lower levels of all three markers, CAF-74 had less α-SMA, slightly more FSP1 and over 10-fold more FAP.
For the CAF-TEM1-intensity, the TEM1-expression level of CAF was classified into four categories (grade 0, grade 1, grade 2, and grade 3) as described in the Materials and Methods section.
Among these fibroblasts, CAFs expressed higher level of IL-6 than did benign NFs. Figure 2 showed that IL-6 secretion from DFs or NFs was significantly less than that from CAFs.
Therefore, in mice treated with the DC-based vaccine in combination with anti-CAF therapy, the level of TGF-β in the TME was significantly decreased, contributing to the effective reduction of Treg cells there.
