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

• Published in: PloS one 2017-08, Vol.12 (8), p.e0182973-e0182973
• Main Authors: Olsson, P Olof, Kalamajski, Sebastian, Maccarana, Marco, Oldberg, Åke, Rubin, Kristofer
• Format: Article
• Language: English
• Subjects: Aberration; Animals; Basic Medicine; Biochemistry; Biology and Life Sciences; Blood vessels; Cancer and Oncology; Cancer och onkologi; Cancer therapies; Cell and Molecular Biology; Cell Line, Tumor; Cell- och molekylärbiologi; Clinical Medicine; Collagen; Collagen - metabolism; Colon; Colon cancer; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Colorectal cancer; Connective tissues; Deoxyribonucleic acid; Development and progression; Disease Models, Animal; DNA; Drug delivery; Drug delivery systems; Extracellular matrix; Fibrillogenesis; Fibromodulin - deficiency; Fibromodulin - genetics; Fluid pressure; Gene expression; Genetic aspects; Glycosaminoglycans - metabolism; Kinases; Klinisk medicin; Macrophages; Medical and Health Sciences; Medical research; Medicin och hälsovetenskap; Medicine; Medicine and Health Sciences; Medicinska och farmaceutiska grundvetenskaper; Mice; Mice, Inbred C57BL; Mucopolysaccharides; Physical Sciences; Physiological aspects; Proteins; Stroma; Tissues; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0182973

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.