title: The nanomechanical signature of breast cancer.
abstract: Cancer initiation and progression follow complex molecular and structural changes in the extracellular matrix and cellular architecture of living tissue. However, it remains poorly understood how the transformation from health to malignancy alters the mechanical properties of cells within the tumour microenvironment. Here, we show using an indentation-type atomic force microscope (IT-AFM) that unadulterated human breast biopsies display distinct stiffness profiles. Correlative stiffness maps obtained on normal and benign tissues show uniform stiffness profiles that are characterized by a single distinct peak. In contrast, malignant tissues have a broad distribution resulting from tissue heterogeneity, with a prominent low-stiffness peak representative of cancer cells. Similar findings are seen in specific stages of breast cancer in MMTV-PyMT transgenic mice. Further evidence obtained from the lungs of mice with late-stage tumours shows that migration and metastatic spreading is correlated to the low stiffness of hypoxia-associated cancer cells. Overall, nanomechanical profiling by IT-AFM provides quantitative indicators in the clinical diagnostics of breast cancer with translational significance.
authors.affiliation: Biozentrum and the Swiss Nanoscience Institute, University of Basel, 4056 Basel, Switzerland.
authors.forename: Marija
authors.initials: M
authors.lastname: Plodinec
authors.forename: Marko
authors.initials: M
authors.lastname: Loparic
authors.forename: Christophe A
authors.initials: CA
authors.lastname: Monnier
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Obermann
authors.forename: Rosanna
authors.initials: R
authors.lastname: Zanetti-Dallenbach
authors.forename: Philipp
authors.initials: P
authors.lastname: Oertle
authors.forename: Janne T
authors.initials: JT
authors.lastname: Hyotyla
authors.forename: Ueli
authors.initials: U
authors.lastname: Aebi
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bentires-Alj
authors.forename: Roderick Y H
authors.initials: RY
authors.lastname: Lim
authors.forename: Cora-Ann
authors.initials: CA
authors.lastname: Schoenenberger
mesh_terms: D000818:Animals; D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000473:pathology*; D015687:Cell Hypoxia; D002465:Cell Movement; D018450:Disease Progression; D004548:Elasticity; D005260:Female; D006244:Hardness; D006801:Humans; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008822:Mice, Transgenic; D018625:Microscopy, Atomic Force / Q000379:methods*