Why do rigid tumors contain soft cancer cells?

ORAL

Abstract

As early as 50 AD, the Roman medical encyclopaedist Celsus recognized that solid tumors are stiffer than surrounding tissue. However, cancer cell lines are softer, which facilitates invasion. This paradox raises several questions: Does softness emerge from adaptation to mechanical and chemical cues in the external microenvironment? Or are soft cells already present inside a rigid primary tumor? We investigate primary samples from patients with mammary and cervical carcinomas on multiple length scales from tissue level down to single cells. We show that primary tumors a highly heterogeneous in their mechanical properties on the tissue level as well as cells do exhibit a broad distribution of rigidities, with a higher fraction of softer and more elongated cells compared to normal tissue. Mechanical modelling based on patient data reveals that tumors remain solid containing a significant fraction of very soft cells. Moreover, it predicts that in such tissues, softer cells spontaneously self-organize into multicellular streams, which we observe experimentallz.

*DFG: KA1116/9-1, KA1116/17-1; EU Horizion 2020: "FORCE"; BMBF 13N9366; NSF award ACI-1341006

Presenters

  • Thomas Fuhs

    • Soft Matter Physics Division, University of Leipzig

Authors

  • Thomas Fuhs

    • Soft Matter Physics Division, University of Leipzig
  • Franziska Wetzel

    • Soft Matter Physics Division, University of Leipzig
  • Anatol W Fritsch

    • Soft Matter Physics Division, University of Leipzig
  • Dapeng Bi

    • Northeastern University
    • Department of Physics, Northeastern University
  • Roland Stange

    • Soft Matter Physics Division, University of Leipzig
  • Steve Pawlizak

    • Soft Matter Physics Division, University of Leipzig
  • Tobias Kiessling

    • Soft Matter Physics Division, University of Leipzig
  • Erik Morawetz

    • Soft Matter Physics Division, University of Leipzig
  • Steffen Grosser

    • Soft Matter Physics Division, University of Leipzig
  • Frank Sauer

    • Soft Matter Physics Division, University of Leipzig
  • Jürgen Lippoldt

    • Soft Matter Physics Division, University of Leipzig
  • Fred Renner

    • Soft Matter Physics Division, University of Leipzig
  • Sabrina Friebe

    • Soft Matter Physics Division, University of Leipzig
  • Mareike Zink

    • Soft Matter Physics Division, University of Leipzig
  • Lars-Christian Horn

    • Division of Gynecologic, Breast and Perinatal Pathology, Universtiy Hospital Leipzig
  • Bahriye Aktas

    • Department of Gynecology, University Hospital Leipzig
  • Klaus Bendrat

    • Pathology Hamburg-West
  • Maja Oktay

    • Montefiore Medical Center
  • Axel Niendorf

    • Pathology Hamburg-West
  • John S Condeelis

    • Albert Einstein College of Medicine
  • Michael Höckel

    • Department of Gynecology, University Hospital Leipzig
  • M Cristina Marchetti

    • Department of Physics, University of California, Santa Barbara
    • University of California, Santa Barbara
    • Physics, University of California, Santa Barbara
    • Physics, UC Santa Barbara
    • University of California Santa Barbara
    • Department of Physics, University of California Santa Barbara
    • Department of Physics, Syracuse University
  • M. Lisa Manning

    • Syracuse University
    • Physics, Syracuse University
    • Department of Physics, Syracuse University
  • Josef Alfons Kaes

    • Univ Leipzig
    • Soft Matter Physics Division, University of Leipzig