Fibromodulin deficiency reduces collagen structural network but not glycosaminoglycan content in a syngeneic model of colon carcinoma

Abstract

Tumor barrier function in carcinoma represents a major challenge to treatment and is therefore an attractive target for increasing drug delivery. Variables related to tumor barrier include aberrant blood vessels, high interstitial fluid pressure, and the composition and structure of the extracellular matrix. One of the proteins associated with dense extracellular matrices is fibromodulin, a collagen fibrillogenesis modulator expressed in tumor stroma but scarce in normal loose connective tissues. Here, we investigated the effects of fibromodulin on stroma ECM in a syngeneic murine colon carcinoma model. We show that fibromodulin deficiency decreased collagen fibril thickness but glycosaminoglycan content and composition were unchanged. Furthermore, vascular density, pericyte coverage and macrophage amount were unaffected. Fibromodulin can therefore be a unique effector of dense collagen matrix assembly in tumor stroma and, without affecting other major matrix components or the cellular composition, can function as a main agent in tumor barrier function.

Hippocampal differential expression underlying the neuroprotective effect of delta-9-tetrahydrocannabinol microdose on old mice

“…Fibromodulin (Fmod) is another gene with age-dependent down-regulation ( Roughley et al, 1996 ) that was upregulated in the old group days after THC treatment ( Figure 3B ). The expression of the collagen genes, Col1a2 and Col1a1, known to be regulated by Olsson et al (2017) , and directly interact with Fmod ( Kalamajski et al, 2016 ), also exhibited the same upregulation. The thyroid hormone receptor β gene (Thrb) is an additional gene with age-dependent decline in expression ( Pawlik-Pachucka et al, 2018 ), which was significantly upregulated as a result of THC treatment.…”

The heterogenic tumor microenvironment of hepatocellular carcinoma and prognostic analysis based on tumor neo-vessels, macrophages and α-SMA

“…The thickness of infiltrating stroma marked by α-SMA was measured to evaluate the depth between tumor nests. For determining the density of infiltrating macrophages, neo-vessels density and thickness of the stroma, the cutoff value to classify subgroups was 270, 215 and 238.6 µm respectively ( 26 ), according to the mean value.…”

Fibromodulin, a Multifunctional Matricellular Modulator

“…Moreover, upregulation of FMOD was described in B-cell chronic lymphocytic leukemia (Pourhanifeh et al 2019). Thus, FMOD is considered a target for treating the cancerous diseases mentioned above and holds the potential to treat other tumor conditions, such as colon carcinoma (Olsson et al 2017). High FMOD expression is also associated with malignancy, as seen in glioblastoma and prostate cancer.…”