Tenascin-C increases lung metastasis by impacting blood vessel invasions.

Tenascin-C increases lung metastasis by impacting blood vessel invasions. Matrix Biol. 2019 Jul 06;: Authors: Sun Z, Velázquez-Quesada I, Murdamoothoo D, Ahowesso C, Yilmaz A, Spenlé C, Averous G, Erne W, Oberndorfer F, Oszwald A, Kain R, Bourdon C, Mangin P, Deligne C, Midwood K, Abou-Faycal C, Lefebvre O, Klein A, van der Heyden M, Chenard MP, Christofori G, Mathelin C, Loustau T, Hussenet T, Orend G Abstract Metastasis is a major cause of death in cancer patients. The extracellular matrix molecule tenascin-C is a known promoter of metastasis, however the underlying mechanisms are not well understood. To further analyze the impact of tenascin-C on cancer progression we generated MMTV-NeuNT mice that develop spontaneous mammary tumors, on a tenascin-C knockout background. We also developed a syngeneic orthotopic model in which tumor cells derived from a MMTV-NeuNT tumor. Tumor cells were transfected with control shRNA or with shRNA to knockdown tenascin-C expression and, were grafted into the mammary gland of immune competent, wildtype or tenascin-C knockout mice. We show that stromal-derived TNC increases metastasis by reducing apoptosis and inducing the cellular plasticity of cancer cells located in pulmonary blood vessels invasions (BVI), before extravasation. We characterized BVI as organized structures of tightly packed aggregates of proliferating tumor cells with epithelial characteristics, surrounded by Fsp1+ cells, interna...
Source: Matrix Biology - Category: Molecular Biology Authors: Tags: Matrix Biol Source Type: research