Stroma properties affect carcinoma physiology and direct malignant cell development. Here we present data showing that alphaVbeta3 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 beta3-deficient compared to wild-type BALB/c mice. Integrin beta3-deficiency had no effect on carcinoma growth rate or on vascular morphology and function. Analyses by electron microscopy of carcinomas from integrin beta3-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 beta3-deficient mice. The fibrotic extracellular matrix (ECM) did not correlate with increased macrophage infiltration in integrin beta3-deficient mice bearing CT26 tumors, indicating that the fibrotic phenotype was not mediated by increased inflammation. In conclusion, we report that integrin beta3-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. © 2012 Friman et al.
T., F., R., G., L.B., S., J., C., N.-E., H., R.K., R., & A., O. (2012). Increased fibrosis and interstitial fluid pressure in two different types of syngeneic murine carcinoma grown in integrin beta3-subunit deficient mice. PLoS ONE. K. Rubin, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. E-mail: Kristofer.Rubin@imbim.uu.se: Public Library of Science (185 Berry Street, Suite 1300, San Francisco CA 94107, United States). Retrieved from http://www.plosone.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0034082&representation=PDF