A convolutional neural network STIFMap reveals associations between stromal stiffness and EMT in breast cancer.

Autor: Stashko C; Department of Surgery, University of California, San Francisco, CA, USA.; Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, San Francisco, CA, USA., Hayward MK; Department of Surgery, University of California, San Francisco, CA, USA.; Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, San Francisco, CA, USA., Northey JJ; Department of Surgery, University of California, San Francisco, CA, USA.; Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, San Francisco, CA, USA., Pearson N; Harvey Mudd College, Claremont, CA, USA., Ironside AJ; Department of Pathology, Western General Hospital, NHS Lothian, Edinburgh, UK., Lakins JN; Department of Surgery, University of California, San Francisco, CA, USA.; Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, San Francisco, CA, USA., Oria R; Department of Surgery, University of California, San Francisco, CA, USA.; Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, San Francisco, CA, USA., Goyette MA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Mayo L; Department of Cell and Tissue Biology, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA., Russnes HG; Department of Pathology and Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Institute for Clinical Medicine, University of Oslo, Oslo, Norway., Hwang ES; Department of Surgery, Duke University Medical Center, Durham, NC, USA., Kutys ML; Department of Cell and Tissue Biology, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA.; UCSF Helen Diller Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA., Polyak K; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Weaver VM; Department of Surgery, University of California, San Francisco, CA, USA. valerie.weaver@ucsf.edu.; Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, San Francisco, CA, USA. valerie.weaver@ucsf.edu.; UCSF Helen Diller Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA. valerie.weaver@ucsf.edu.; Department of Radiation Oncology, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA. valerie.weaver@ucsf.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Jun 15; Vol. 14 (1), pp. 3561. Date of Electronic Publication: 2023 Jun 15.
DOI: 10.1038/s41467-023-39085-1
Abstrakt: Intratumor heterogeneity associates with poor patient outcome. Stromal stiffening also accompanies cancer. Whether cancers demonstrate stiffness heterogeneity, and if this is linked to tumor cell heterogeneity remains unclear. We developed a method to measure the stiffness heterogeneity in human breast tumors that quantifies the stromal stiffness each cell experiences and permits visual registration with biomarkers of tumor progression. We present Spatially Transformed Inferential Force Map (STIFMap) which exploits computer vision to precisely automate atomic force microscopy (AFM) indentation combined with a trained convolutional neural network to predict stromal elasticity with micron-resolution using collagen morphological features and ground truth AFM data. We registered high-elasticity regions within human breast tumors colocalizing with markers of mechanical activation and an epithelial-to-mesenchymal transition (EMT). The findings highlight the utility of STIFMap to assess mechanical heterogeneity of human tumors across length scales from single cells to whole tissues and implicates stromal stiffness in tumor cell heterogeneity.
(© 2023. The Author(s).)
Databáze: MEDLINE
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