Tumor-Associated macrophages (TAMs) form an interconnected cellular supportive network in anaplastic thyroid carcinoma

Bernard Caillou, Monique Talbot, Sossou Weyemi, Catherine Pioche-Durieu, Abir Ghuzlan, Jean Michel Bidart, Salem Chouaib, Martin Schlumberger, Corinne Dupuy

Research output: Contribution to journalArticle

Abstract

Background: A relationship between the increased density of tumor-associated macrophages (TAMs) and decreased survival was recently reported in thyroid cancer patients. Among these tumors, anaplastic thyroid cancer (ATC) is one of the most aggressive solid tumors in humans. TAMs (type M2) have been recognized as promoting tumor growth. The purpose of our study was to analyze with immunohistochemistry the presence of TAMs in a series of 27 ATC. Methodology/Principal Findings: Several macrophages markers such as NADPH oxidase complex NOX2-p22phox, CD163 and CD 68 were used. Immunostainings showed that TAMs represent more than 50% of nucleated cells in all ATCs. Moreover, these markers allowed the identification of elongated thin ramified cytoplasmic extensions, bestowing a "microglia-like" appearance on these cells which we termed "Ramified TAMs" (RTAMs). In contrast, cancer cells were totally negative. Cellular stroma was highly simplified since apart from cancer cells and blood vessels, RTAMs were the only other cellular component. RTAMs were evenly distributed and intermingled with cancer cells, and were in direct contact with other RTAMs via their ramifications. Moreover, RTAMs displayed strong immunostaining for connexin Cx43. Long chains of interconnected RTAMs arose from perivascular clusters and were dispersed within the tumor parenchyma. When expressed, the glucose transporter Glut1 was found in RTAMs and blood vessels, but rarely in cancer cells. Conclusion: ATCs display a very dense network of interconnected RTAMs in direct contact with intermingled cancer cells. To our knowledge this is the first time that such a network is described in a malignant tumor. This network was found in all our studied cases and appeared specific to ATC, since it was not found in differentiated thyroid cancers specimens. Taken together, these results suggest that RTAMs network is directly related to the aggressiveness of the disease via metabolic and trophic functions which remain to be determined.

Original languageEnglish (US)
Article numbere22567
JournalPLoS One
Volume6
Issue number7
DOIs
StatePublished - 2011
Externally publishedYes

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Macrophages
carcinoma
Tumors
macrophages
neoplasms
Neoplasms
Cells
Blood vessels
direct contact
blood vessels
Anaplastic Thyroid Carcinoma
Thyroid Neoplasms
connexins
glucose transporters
Connexin 43
Connexins
Blood Vessels
Facilitative Glucose Transport Proteins
NADPH Oxidase
neuroglia

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Tumor-Associated macrophages (TAMs) form an interconnected cellular supportive network in anaplastic thyroid carcinoma. / Caillou, Bernard; Talbot, Monique; Weyemi, Sossou; Pioche-Durieu, Catherine; Ghuzlan, Abir; Bidart, Jean Michel; Chouaib, Salem; Schlumberger, Martin; Dupuy, Corinne.

In: PLoS One, Vol. 6, No. 7, e22567, 2011.

Research output: Contribution to journalArticle

Caillou, B, Talbot, M, Weyemi, S, Pioche-Durieu, C, Ghuzlan, A, Bidart, JM, Chouaib, S, Schlumberger, M & Dupuy, C 2011, 'Tumor-Associated macrophages (TAMs) form an interconnected cellular supportive network in anaplastic thyroid carcinoma', PLoS One, vol. 6, no. 7, e22567. https://doi.org/10.1371/journal.pone.0022567
Caillou, Bernard ; Talbot, Monique ; Weyemi, Sossou ; Pioche-Durieu, Catherine ; Ghuzlan, Abir ; Bidart, Jean Michel ; Chouaib, Salem ; Schlumberger, Martin ; Dupuy, Corinne. / Tumor-Associated macrophages (TAMs) form an interconnected cellular supportive network in anaplastic thyroid carcinoma. In: PLoS One. 2011 ; Vol. 6, No. 7.
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AU - Caillou, Bernard

AU - Talbot, Monique

AU - Weyemi, Sossou

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AU - Ghuzlan, Abir

AU - Bidart, Jean Michel

AU - Chouaib, Salem

AU - Schlumberger, Martin

AU - Dupuy, Corinne

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