A bulky glycocalyx fosters metastasis formation by promoting G1 cell cycle progression.

Autor: Woods EC; Department of Chemistry, Stanford University, California, United States., Kai F; Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, San Francisco, United States., Barnes JM; Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, San Francisco, United States., Pedram K; Department of Chemistry, Stanford University, California, United States., Pickup MW; Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, San Francisco, United States., Hollander MJ; Department of Chemistry, Stanford University, California, United States., Weaver VM; Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, San Francisco, United States.; Department of Anatomy, University of California, San Francisco, San Francisco, United States.; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, United States.; Department of Radiation Oncology, University of California, San Francisco, San Francisco, United States.; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, United States.; UCSF Helen Diller Comprehensive Cancer Center, University of California, San Francisco, San Francisco, United States., Bertozzi CR; Department of Chemistry, Stanford University, California, United States.; Howard Hughes Medical Institute, Stanford University, California, United States.
Jazyk: angličtina
Zdroj: ELife [Elife] 2017 Dec 21; Vol. 6. Date of Electronic Publication: 2017 Dec 21.
DOI: 10.7554/eLife.25752
Abstrakt: Metastasis depends upon cancer cell growth and survival within the metastatic niche. Tumors which remodel their glycocalyces, by overexpressing bulky glycoproteins like mucins, exhibit a higher predisposition to metastasize, but the role of mucins in oncogenesis remains poorly understood. Here we report that a bulky glycocalyx promotes the expansion of disseminated tumor cells in vivo by fostering integrin adhesion assembly to permit G1 cell cycle progression. We engineered tumor cells to display glycocalyces of various thicknesses by coating them with synthetic mucin-mimetic glycopolymers. Cells adorned with longer glycopolymers showed increased metastatic potential, enhanced cell cycle progression, and greater levels of integrin-FAK mechanosignaling and Akt signaling in a syngeneic mouse model of metastasis. These effects were mirrored by expression of the ectodomain of cancer-associated mucin MUC1. These findings functionally link mucinous proteins with tumor aggression, and offer a new view of the cancer glycocalyx as a major driver of disease progression.
Databáze: MEDLINE