2020
DOI: 10.3390/gels6040033
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Matrix Remodeling and Hyaluronan Production by Myofibroblasts and Cancer-Associated Fibroblasts in 3D Collagen Matrices

Abstract: The tumor microenvironment is a key modulator in cancer progression and has become a novel target in cancer therapy. An increase in hyaluronan (HA) accumulation and metabolism can be found in advancing tumor progression and are often associated with aggressive malignancy, drug resistance and poor prognosis. Wound-healing related myofibroblasts or activated cancer-associated fibroblasts (CAF) are assumed to be the major sources of HA. Both cell types are capable to synthesize new matrix components as well as re… Show more

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Cited by 26 publications
(26 citation statements)
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References 79 publications
(118 reference statements)
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“…On this focus, increasing evidence suggests that stromal cells are the main players in fibrotic ECM production. [ 28–30 ] In order to evaluate the capacity of 3D STAMS to recapitulate the desmoplastic reaction and ECM deposition found in human pancreatic tumors, collagen and glycosaminoglycans (GAGs) were quantified. As demonstrated in Figure , both 3D co‐culture models showed an increased collagen secretion than their monoculture counterparts, highlighting the role of CAFs in fibrotic stroma production.…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…On this focus, increasing evidence suggests that stromal cells are the main players in fibrotic ECM production. [ 28–30 ] In order to evaluate the capacity of 3D STAMS to recapitulate the desmoplastic reaction and ECM deposition found in human pancreatic tumors, collagen and glycosaminoglycans (GAGs) were quantified. As demonstrated in Figure , both 3D co‐culture models showed an increased collagen secretion than their monoculture counterparts, highlighting the role of CAFs in fibrotic stroma production.…”
Section: Resultsmentioning
confidence: 99%
“…Such includes the accumulation of hyaluronic acid (HA), a large linear glycosaminoglycan composed of D‐glucuronic and N ‐acetyl‐D‐glucosamine that is reportedly to be overexpressed in PDAC. [ 29 ] Similar to collagen, GAGs quantification showed higher GAGs content in co‐culture models than monoculture systems. Moreover, GAGs deposition is slightly higher in STAMS than in Random microtissues (Figure 5B day 14).…”
Section: Resultsmentioning
confidence: 99%
“…Activated CAFs promote tumor growth and metastasis through multiple mechanisms, such as ECM remodeling, secretion of cytokines, and immunosuppression [ 12 ]. Activation of CAFs also contributes to the stiffening of TME by matrix remodeling, including increased secretion of enzymes, excess deposition of ECM (e.g., HA) [ 14 , 15 , 16 ], and force-mediated matrix remodeling [ 17 , 18 ]. In particular, secretion of matrix metalloproteinase (MMP) by CAFs contributes to the matrix remodeling and cell invasion by forming “tracks” in the ECM, hence facilitating cancer cell migration [ 17 ].…”
Section: Tumor Microenvironment In Pancreatic Ductal Adenocarcinommentioning
confidence: 99%
“…More intriguingly, HAS-1 expression in ACC tumor cells was associated with a lower mitotic rate, a lower prevalence of atypical mitotic figures and a better outcome. The prognostic significance of HAS-1 in cancers is equivocal and has been studied either in cancer cells or in cancer stroma, including cancer-associated fibroblasts [ 52 , 53 , 54 ]. However, in agreement with our findings, a negative prognostic role of HAS-1 downregulation in cancer cells has been described in lung cancer [ 55 ] and melanoma [ 56 ].…”
Section: Discussionmentioning
confidence: 99%