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  • Pietila, EA (author)

Co-evolution of matrisome and adaptive adhesion dynamics drives ovarian cancer chemoresistance

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2021-06-23
  • Springer Science and Business Media LLC,2021

Numbers

  • LIBRIS-ID:oai:prod.swepub.kib.ki.se:147104942
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:147104942URI
  • https://doi.org/10.1038/s41467-021-24009-8DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Due to its dynamic nature, the evolution of cancer cell-extracellular matrix (ECM) crosstalk, critically affecting metastasis and treatment resistance, remains elusive. Our results show that platinum-chemotherapy itself enhances resistance by progressively changing the cancer cell-intrinsic adhesion signaling and cell-surrounding ECM. Examining ovarian high-grade serous carcinoma (HGSC) transcriptome and histology, we describe the fibrotic ECM heterogeneity at primary tumors and distinct metastatic sites, prior and after chemotherapy. Using cell models from systematic ECM screen to collagen-based 2D and 3D cultures, we demonstrate that both specific ECM substrates and stiffness increase resistance to platinum-mediated, apoptosis-inducing DNA damage via FAK and β1 integrin-pMLC-YAP signaling. Among such substrates around metastatic HGSCs, COL6 was upregulated by chemotherapy and enhanced the resistance of relapse, but not treatment-naïve, HGSC organoids. These results identify matrix adhesion as an adaptive response, driving HGSC aggressiveness via co-evolving ECM composition and sensing, suggesting stromal and tumor strategies for ECM pathway targeting.

Added entries (persons, corporate bodies, meetings, titles ...)

  • Gonzalez-Molina, JKarolinska Institutet (author)
  • Moyano-Galceran, LKarolinska Institutet (author)
  • Jamalzadeh, S (author)
  • Zhang, K (author)
  • Lehtinen, L (author)
  • Turunen, SP (author)
  • Martins, TA (author)
  • Gultekin, OKarolinska Institutet (author)
  • Lamminen, T (author)
  • Kaipio, K (author)
  • Joneborg, UKarolinska Institutet (author)
  • Hynninen, J (author)
  • Hietanen, S (author)
  • Grenman, S (author)
  • Lehtonen, R (author)
  • Hautaniemi, S (author)
  • Carpen, O (author)
  • Carlson, JWKarolinska Institutet (author)
  • Lehti, KKarolinska Institutet (author)
  • Karolinska Institutet (creator_code:org_t)

Related titles

  • In:Nature communications: Springer Science and Business Media LLC12:1, s. 3904-2041-1723

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