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Deciphering the cells of origin of squamous cell carcinomas

Nature Reviews Cancer volume 18, pages 549–561 (2018)Cite this article

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Abstract

Squamous cell carcinomas (SCCs) are among the most prevalent human cancers. SCC comprises a wide range of tumours originated from diverse anatomical locations that share common genetic mutations and expression of squamous differentiation markers. SCCs arise from squamous and non-squamous epithelial tissues. Here, we discuss the different studies in which the cell of origin of SCCs has been uncovered by expressing oncogenes and/or deleting tumour suppressor genes in the different cell lineages that compose these epithelia. We present evidence showing that the squamous differentiation phenotype of the tumour depends on the type of mutated oncogene and the cell of origin, which dictate the competence of the cells to initiate SCC formation, as well as on the aggressiveness and invasive properties of these tumours.

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Fig. 1: Lineage tracing and the cells of origin of cancer.
Fig. 2: Architecture and cellular hierarchy present in the tissues from which SCC arise.
Fig. 3: Common genetic alterations found in the different types of SCC.
Fig. 4: The cells at the origin of CSCC.
Fig. 5: The cells of origin in HNSCC and ESCC.
Fig. 6: SOX2 promotes LSCC differentiation irrespective of the cell of origin.

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Acknowledgements

C.B. is an investigator of WELBIO. A.S.-D. is supported by a fellowship of the Belgian Fund for Scientific Research (FNRS). CB is supported by the FNRS, the Fondation contre le Cancer, the Université Libre de Bruxelles Fondation, the Fondation Baillet Latour, Worldwide Cancer Research and a consolidator grant from the European Research Council.

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  1. Université Libre de Bruxelles, Laboratory of Stem Cells and Cancer, Brussels, Belgium

    Adriana Sánchez-Danés & Cédric Blanpain

  2. WELBIO, Université Libre de Bruxelles, Brussels, Belgium

    Cédric Blanpain

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  1. Adriana Sánchez-Danés
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Both authors read the literature, discussed the contents of the Review and wrote the article.

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Glossary

Squamous cell carcinomas

(SCCs). Cancers that present squamous differentiation, which is visible by the presence of keratin materials.

Lineage tracing

A method involving experiments that enable the labelling of a cell or a group of cells and assess the fate of these labelled cells and their progeny over time.

Stem cells

Cells that are at the top of the cellular hierarchy and are characterized by long-term self-renewing capacity and give rise to progenitors, transit-amplifying cells and differentiated cells.

Progenitors

Cells that can self-renew and give rise to terminally differentiated cells. Depending on the proportion of asymmetric and symmetric divisions, progenitors can live long term or short term.

Stratified squamous epithelium

Epithelium composed of a layer of basal proliferative cells and several suprabasal layers of differentiated cells that express keratins and progressively flatten near the surface, eventually presenting as enucleated cells that are shed from the surface. These amorphous keratinized ghost cells are known as squames. The inner surface of the body is lined with non-keratinized stratified squamous epithelium, which is characterized by superficial cells that are flattened and nucleated.

Keratin pearls

Keratin-derived amorphous materials arising from the differentiation of tumour cells.

Transit-amplifying cells

Cells that divide a finite number of times and then terminally differentiate.

Clonal analysis

The study of the fate, renewal and long-term maintenance of single isolated cells over time.

Dedifferentiation

A process that occurs when committed or differentiated cells revert to a less committed state.

Secretory cells

Cells of the airway system (also known as Clara cells) that produce mucins and antimicrobial peptides.

Ciliated cells

Cells that contain tiny hair-like structures on their surface called cilia. Ciliated cells of the airway system propel debris and dirty mucus out of the respiratory tract through the movement of their cilia.

Type 1 cells

(AT1 cells). Cells of the alveolar epithelium that enable gas exchange.

Type 2 cells

(AT2 cells). Cells of the alveolar epithelium that produce surfactant, which helps the alveolar structure to stay open and thus enables gas exchange.

Lineage ablation

The selective killing of a cell lineage, which is usually performed by inducing expression of a toxin or a toxin receptor in a cell of interest and then administering that toxin.

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Sánchez-Danés, A., Blanpain, C. Deciphering the cells of origin of squamous cell carcinomas. Nat Rev Cancer 18, 549–561 (2018). https://doi.org/10.1038/s41568-018-0024-5

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