Activation of fibroblasts in cancer stroma

Chemokines in tumor development and progression

“…The anti-angiogenic effects of these chemokines are mediated by a common receptor, CXCR3 (Figure 2). Moreover, the Duffy antigen, which can sequester the ELR motif-positive CXC chemokines without eliciting any intracellular signals (Table 1), has been shown to suppress the angiogenic effects of the ELR-positive CXC chemokines [68]. Thus, the balance between pro-angiogenic and anti-angiogenic chemokines may determine the degree of tumor neovascularization.…”

From sentinel cells to inflammatory culprits: cancer‐associated fibroblasts in tumour‐related inflammation

“…While the distinct functional characteristics of the various CAF subsets are poorly defined, their role in supporting tumour growth has been established: CAFs have been found to promote tumour growth by directly stimulating tumour cell proliferation via secreted growth factors, and by enhancing angiogenesis [17][18][19]. Enhancement of tumour angiogenesis by CAFs can be mediated either directly, by secreting pro-angiogenic factors including interleukin (IL)-8/CXCL8, vascular endothelial growth factor (VEGF), and fibroblast growth factor (FGF)-2, or indirectly, by secreting extracellular matrix (ECM)-remodelling proteases, such as matrix metalloproteinase (MMP)-9, MMP-13, and MMP-14 that activate a multitude of latent soluble and insoluble factors with diverse activities [7,[20][21][22]. In addition, CAFs foster tumour progression and metastasis by modifying the architecture of the ECM, by enhancing deposition of collagen, and by mediating increased cross-linking of collagen fibres, thus stiffening stroma.…”

“…Such aberrant fibrotic responses, termed desmoplasia, correlate with tumour progression and poor prognosis in some cancer types [23]. These non-inflammatory tumourpromoting effects of CAFs have been recently reviewed [22,26,27]. The focus of this review is on pathways by which CAFs mediate tumour-promoting inflammation and modulate the components of the inflammatory microenvironment that facilitate tumour initiation, progression, and metastasis.…”

Exosomes in colorectal carcinoma formation: ALIX under the magnifying glass

“…1,6,17,18 CAFs as key factors of abnormal epithelial-stromal interaction and their powerful tumor-supportive effect (eg, increased regulator ligand and extracellular matrix molecule expression) are well known compared with normal stromal cells with similar morphology, that is, subepithelial myofibroblasts. [18][19][20] Tumor cellreleased exosomes are also detectable in the circulation where the plasma level of their specific proteins (eg, CD63 and tumor susceptibility gene 101/TSG101) and miRNA content may be useful as diagnostic and/or prognostic markers in different tumor types including colorectal carcinomas. [21][22][23][24] Our study was designed to analyze the top exosome-specific markers based on change of their tissue mRNA level during colorectal adenomacarcinoma sequence.…”