title: Lymph node biophysical remodeling is associated with melanoma lymphatic drainage.
abstract: Tissue remodeling is a characteristic of many solid tumor malignancies including melanoma. By virtue of tumor lymphatic transport, remodeling pathways active within the local tumor microenvironment have the potential to be operational within lymph nodes (LNs) draining the tumor interstitium. Here, we show that lymphatic drainage from murine B16 melanomas in syngeneic, immune-competent C57Bl/6 mice is associated with LN enlargement as well as nonuniform increases in bulk tissue elasticity and viscoelasticity, as measured by the response of whole LNs to compression. These remodeling responses, which quickly manifest in tumor-draining lymph nodes (TDLNs) after tumor inoculation and before apparent metastasis, were accompanied by changes in matrix composition, including up to 3-fold increases in the abundance of soluble collagen and hyaluronic acid. Intranodal pressures were also significantly increased in TDLNs (+1 cmH2O) relative to both non-tumor-draining LNs (-1 cmH2O) and LNs from naive animals (-1 to 2 cmH2O). These data suggest that the reorganization of matrix structure, composition, and fluid microenvironment within LNs associated with tumor lymphatic drainage parallels remodeling seen in primary malignancies and has the potential to regulate the adhesion, proliferation, and signaling function of LN-resident cells involved in directing melanoma disease progression.
authors.affiliation: George W. Woodruff School of Mechanical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA; and Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.
authors.forename: Nathan Andrew
authors.initials: NA
authors.lastname: Rohner
authors.affiliation: George W. Woodruff School of Mechanical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA; and Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: McClain
authors.affiliation: George W. Woodruff School of Mechanical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA; and Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.
authors.forename: Sara Lydia
authors.initials: SL
authors.lastname: Tuell
authors.affiliation: George W. Woodruff School of Mechanical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA; and Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Warner
authors.affiliation: George W. Woodruff School of Mechanical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA; and Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.
authors.forename: Blair
authors.initials: B
authors.lastname: Smith
authors.affiliation: George W. Woodruff School of Mechanical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA; and Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.
authors.forename: Youngho
authors.initials: Y
authors.lastname: Yun
authors.affiliation: George W. Woodruff School of Mechanical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA; and Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Mohan
authors.affiliation: George W. Woodruff School of Mechanical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA; and Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.
authors.forename: Manuela
authors.initials: M
authors.lastname: Sushnitha
authors.affiliation: George W. Woodruff School of Mechanical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA; and Winship Cancer Institute, Emory University, Atlanta, Georgia, USA susan.thomas@gatech.edu.
authors.forename: Susan Napier
authors.initials: SN
authors.lastname: Thomas
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D015398:Signal Transduction; D059016:Tumor Microenvironment
keywords: cancer; sentinel lymph node; tissue mechanical properties