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Open AccessArticle

Cancer Associated Fibroblasts and Senescent Thyroid Cells in the Invasive Front of Thyroid Carcinoma

1
Molecular Mechanisms Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
2
Laboratory of Molecular Pathology, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
3
Hematology, Fondazione Cà Granda IRCCS Policlinico, 20122 Milan, Italy
4
Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
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Soft Tissue and Bone Pathology, Histopathology and Pediatric Pathology Unit, Department of Diagnostic Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
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Platform of Integrated Biology, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
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School of Medicine, Università degli Studi di Milano, 20122 Milan, Italy
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Human Tumors Immunobiology Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
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Department of Oncology and Hemato-oncology, University of Milan, 20122 Milan, Italy
*
Authors to whom correspondence should be addressed.
Co-last authors.
Cancers 2020, 12(1), 112; https://doi.org/10.3390/cancers12010112
Received: 12 December 2019 / Accepted: 27 December 2019 / Published: 1 January 2020
(This article belongs to the Special Issue Thyroid Cancer)
Thyroid carcinoma (TC) comprises several histotypes with different aggressiveness, from well (papillary carcinoma, PTC) to less differentiated forms (poorly differentiated and anaplastic thyroid carcinoma, PDTC and ATC, respectively). Previous reports have suggested a functional role for cancer-associated fibroblasts (CAFs) or senescent TC cells in the progression of PTC. In this study, we investigated the presence of CAFs and senescent cells in proprietary human TCs including PTC, PDTC, and ATC. Screening for the driving lesions BRAFV600E and N/H/KRAS mutations, and gene fusions was also performed to correlate results with tumor genotype. In samples with unidentified drivers, transcriptomic profiles were used to establish a BRAF- or RAS-like molecular subtype based on a gene signature derived from The Cancer Genome Atlas. By using immunohistochemistry, we found co-occurrence of stromal CAFs and senescent TC cells at the tumor invasive front, where deposition of collagen (COL1A1) and expression of lysyl oxidase (LOX) enzyme were also detected, in association with features of local invasion. Concurrent high expression of CAFs and of the senescent TC cells markers, COL1A1 and LOX was confirmed in different TC histotypes in proprietary and public gene sets derived from Gene Expression Omnibus (GEO) repository, and especially in BRAF mutated or BRAF-like tumors. In this study, we show that CAFs and senescent TC cells co-occur in various histotypes of BRAF-driven thyroid tumors and localize at the tumor invasive front. View Full-Text
Keywords: thyroid cancer; CAFs; senescent cells; BRAFV600E; BRAF- and RAS-like signaling thyroid cancer; CAFs; senescent cells; BRAFV600E; BRAF- and RAS-like signaling
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Minna, E.; Brich, S.; Todoerti, K.; Pilotti, S.; Collini, P.; Bonaldi, E.; Romeo, P.; De Cecco, L.; Dugo, M.; Perrone, F.; Busico, A.; Vingiani, A.; Bersani, I.; Anichini, A.; Mortarini, R.; Neri, A.; Pruneri, G.; Greco, A.; Borrello, M.G. Cancer Associated Fibroblasts and Senescent Thyroid Cells in the Invasive Front of Thyroid Carcinoma. Cancers 2020, 12, 112.

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