Figure 3.

Correlating mechanical properties and ECM reorganization during human breast cancer progression. Stiffness distribution and respective H&E stained sections (A) of normal mammary gland tissue (top), benign lesion (middle) and malignant tumor (bottom). Stiffness distribution of normal breast tissue is unimodal and the histology shows the terminal ductal lobular unit of a normal mammary gland fenced by interstitial connective tissue. A benign lesion reveals a unimodal, but broader stiffness distribution with an increase in stiffness compared with the healthy sample. The histology of benign lesions reveals extensive fibrotic stroma interspersed with fibroblasts typical for fibroadenoma. Invasive cancer shows heterogeneous stiffness distribution with a characteristic soft peak, where the histology shows an invasive breast carcinoma with infiltrating nests of cancer cells that have evoked a dense fibrous tissue response. Scale bar applies to all images, 50 μm. The distinct ECM stiffness and structure of late MMTV-PyMT cancer was probed by atomic force microscopy (B) and immunohistochemistry (C). Gradual stiffening from the core to the periphery was observed. Mechanical heterogeneity increased and is most extensive at the periphery (B). While collagen type I and laminin-111 were virtually absent in soft tissue (the core), the heterogeneous presentation (brown staining) of collagen type I and laminin-111 was increased at the periphery as evidenced in (C). Scale bar applies to all images, 50 μm. (A–C reproduced with permision from Plodinec et al., 2012).