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| Poster, Friday, 19:00 |
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| Nanomechanical profile of
tumorigenic transformation in human and mouse breast biopsies
Marija Plodinec1, Christophe
A. Monnier1, Ellen Obermann2, Marko Loparic1,
Rosmarie Suetterlin1, Urs Mueller3, Mohamed Bentires-Alj3,
Rosanna Zanetti4, Ueli Aebi5, Roderick Y.H. Lim1,
Cora-Ann Schoenenberger1,5
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1
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Department of Structural Biology
and Biophysics, Biozentrum and Swiss Nanoscience Institute, University
of Basel, Switzerland |
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2
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Department of Pathology, University
Hospital Basel, Switzerland |
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3
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Friedrich Miescher Institute for
Biomedical Research, Basel, Switzerland |
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4
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Department of Gynecology and Gynecological
Oncology, University Hospital Basel, Switzerland |
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5
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Maurice Mueller Institute for Structural
biology, Biozentrum, University of Basel, Switzerland |
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| Contact:
| Website |
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Tumor mechanobiology is an essential prerequisite to understanding cancer
progression. Yet, how the mechanical properties of cells evolve from normal
mammary gland to malignancy and metastasis and manifest themselves at the
tissue level is poorly understood. To address this issue, we have conducted
comprehensive double-blind experiments that correlate the nanomechanical
characteristics of native human breast biopsies to histopathological analysis.
Using the atomic force microscope (AFM) to distinguish between cells and
extracellular matrix (ECM), our results reveal that distinct stiffness
profiles are associated with altered tissue phenotypes. Unlike healthy
or benign tumor tissue, the stiff stromal tissue located at the tumor periphery
softens towards the core in malignant tissue. As further validation, the
stiffness profiles of cancer development and progression obtained from
MMTV-PyMT transgenic mice are almost identical to the human data. Interestingly,
immunohistochemical analyses of malignant tissue indicate direct correlations
between its soft regions and hypoxia. The soft hypoxic cells regions seem
to have increased migration potential late into the cancer and are present
in distant metastatic lesions in murine lungs. Overall, these findings
reveal a direct correlation between hypoxia-related tissue softening, cancer
progression and metastasis. |
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