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Recapitulating thyroid cancer histotypes through engineering embryonic stem cells

Author

Listed:
  • Veronica Veschi

    (University of Palermo)

  • Alice Turdo

    (University of Palermo)

  • Chiara Modica

    (University of Palermo)

  • Francesco Verona

    (University of Palermo)

  • Simone Franco

    (University of Palermo)

  • Miriam Gaggianesi

    (University of Palermo)

  • Elena Tirrò

    (University of Palermo
    University of Catania)

  • Sebastiano Bella

    (University of Palermo)

  • Melania Lo Iacono

    (University of Palermo)

  • Vincenzo Davide Pantina

    (University of Palermo)

  • Gaetana Porcelli

    (University of Palermo)

  • Laura Rosa Mangiapane

    (University of Palermo)

  • Paola Bianca

    (University of Palermo)

  • Aroldo Rizzo

    (Villa Sofia-Cervello Hospital)

  • Elisabetta Sciacca

    (Queen Mary University, Experimental Medicine & Rheumatology)

  • Irene Pillitteri

    (University of Palermo)

  • Veronica Vella

    (University of Catania, Garibaldi-Nesima Hospital)

  • Antonino Belfiore

    (University of Catania, Garibaldi-Nesima Hospital)

  • Maria Rita Bongiorno

    (University of Palermo)

  • Giuseppe Pistone

    (University of Palermo)

  • Lorenzo Memeo

    (Mediterranean Institute of Oncology, Viagrande)

  • Lorenzo Colarossi

    (Mediterranean Institute of Oncology, Viagrande)

  • Dario Giuffrida

    (Mediterranean Institute of Oncology, Viagrande)

  • Cristina Colarossi

    (Mediterranean Institute of Oncology, Viagrande)

  • Paolo Vigneri

    (University of Catania)

  • Matilde Todaro

    (University of Palermo
    University of Palermo)

  • Giorgio Stassi

    (University of Palermo)

Abstract

Thyroid carcinoma (TC) is the most common malignancy of endocrine organs. The cell subpopulation in the lineage hierarchy that serves as cell of origin for the different TC histotypes is unknown. Human embryonic stem cells (hESCs) with appropriate in vitro stimulation undergo sequential differentiation into thyroid progenitor cells (TPCs-day 22), which maturate into thyrocytes (day 30). Here, we create follicular cell-derived TCs of all the different histotypes based on specific genomic alterations delivered by CRISPR-Cas9 in hESC-derived TPCs. Specifically, TPCs harboring BRAFV600E or NRASQ61R mutations generate papillary or follicular TC, respectively, whereas addition of TP53R248Q generate undifferentiated TCs. Of note, TCs arise by engineering TPCs, whereas mature thyrocytes have a very limited tumorigenic capacity. The same mutations result in teratocarcinomas when delivered in early differentiating hESCs. Tissue Inhibitor of Metalloproteinase 1 (TIMP1)/Matrix metallopeptidase 9 (MMP9)/Cluster of differentiation 44 (CD44) ternary complex, in cooperation with Kisspeptin receptor (KISS1R), is involved in TC initiation and progression. Increasing radioiodine uptake, KISS1R and TIMP1 targeting may represent a therapeutic adjuvant option for undifferentiated TCs.

Suggested Citation

  • Veronica Veschi & Alice Turdo & Chiara Modica & Francesco Verona & Simone Franco & Miriam Gaggianesi & Elena Tirrò & Sebastiano Bella & Melania Lo Iacono & Vincenzo Davide Pantina & Gaetana Porcelli &, 2023. "Recapitulating thyroid cancer histotypes through engineering embryonic stem cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36922-1
    DOI: 10.1038/s41467-023-36922-1
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    References listed on IDEAS

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    1. Jane E. Visvader, 2011. "Cells of origin in cancer," Nature, Nature, vol. 469(7330), pages 314-322, January.
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