title: Increased fibrosis and interstitial fluid pressure in two different types of syngeneic murine carcinoma grown in integrin β3-subunit deficient mice.
abstract: Stroma properties affect carcinoma physiology and direct malignant cell development. Here we present data showing that α(V)β(3) expressed by stromal cells is involved in the control of interstitial fluid pressure (IFP), extracellular volume (ECV) and collagen scaffold architecture in experimental murine carcinoma. IFP was elevated and ECV lowered in syngeneic CT26 colon and LM3 mammary carcinomas grown in integrin β(3)-deficient compared to wild-type BALB/c mice. Integrin β(3)-deficiency had no effect on carcinoma growth rate or on vascular morphology and function. Analyses by electron microscopy of carcinomas from integrin β(3)-deficient mice revealed a coarser and denser collagen network compared to carcinomas in wild-type littermates. Collagen fibers were built from heterogeneous and thicker collagen fibrils in carcinomas from integrin β(3)-deficient mice. The fibrotic extracellular matrix (ECM) did not correlate with increased macrophage infiltration in integrin β(3)-deficient mice bearing CT26 tumors, indicating that the fibrotic phenotype was not mediated by increased inflammation. In conclusion, we report that integrin β(3)-deficiency in tumor stroma led to an elevated IFP and lowered ECV that correlated with a more fibrotic ECM, underlining the role of the collagen network for carcinoma physiology.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Friman
authors.forename: Renata
authors.initials: R
authors.lastname: Gustafsson
authors.forename: Linda B
authors.initials: LB
authors.lastname: Stuhr
authors.forename: Jean
authors.initials: J
authors.lastname: Chidiac
authors.forename: Nils-Erik
authors.initials: NE
authors.lastname: Heldin
authors.forename: Rolf K
authors.initials: RK
authors.lastname: Reed
authors.forename: Ake
authors.initials: A
authors.lastname: Oldberg
authors.forename: Kristofer
authors.initials: K
authors.lastname: Rubin
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D003094:Collagen / Q000378:metabolism; D045604:Extracellular Fluid; D005260:Female; D005355:Fibrosis / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006909:Hydroxyproline / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D039661:Integrin beta3 / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D010641:Phenotype; D011312:Pressure
chemical_list: D039302:Integrin alphaVbeta3; D039661:Integrin beta3; D003094:Collagen; D006909:Hydroxyproline