Force characterization of tissue from normal, pre-invasive and invasive breast cancer

Historically, cancer research has focused on understanding the genetic and biochemical regulation of tumor progression while the biomechanical influences have only recently been studied.  Clear evidence has emerged indicating that mechanical forces are closely associated with tumor progression.  In fact, biomechanical cues are integrated with biochemical and genetic cues at every step.  To investigate how micro-environment stiffness may affect progression in human breast tumors, we use atomic force microscopy (AFM) to probe the mechanical properties of tissue from patients diagnosed with various stages of breast cancer.  Using this technique we are able to assess the elastic modulus of the tissue focusing on the border between the tumor epithelium and the surrounding stroma.  Preliminary data indicates that the extracellular matrix surrounding tumors have varying stiffness.  These stiffer areas may be predictive of tumor type and invasiveness.  Coupling these results with immunohistochemistry allows us to determine the nature of these mechanically distinct regions by drawing a correlation between stiffness and collagen cross-linking with localization of LOX.   We are also determining how the tumor epithelium responds to mechanical cues by examining integrin activation and stress fiber formation.