Cancer stem cell regulation changes during skin carcinoma progression to promote metastasis

Researchers from the group of Aging and Cancer, led by Purificación Muñoz in the Institute of Biomedical Research of Bellvitge (IDIBELL) demonstrated that the cancer stem cell features change during the skin squamous cell carcinoma progression to generate highly aggressive and metastasis prone tumors. These results were recently published in Cancer Research journal.

Squamous cell carcinomas are the second most frequent skin tumors. A high percentage of these tumors are treated by surgical excision. However, some advanced carcinomas are recurrent and show an aggressive growth and enhanced metastasis.

Previous studies demonstrated that most of tumors contain a subset of cells, which exhibit similar features to adult stem cells. This population of tumor cells, called cancer stem cells, is responsible for tumor growth and metastasis generation. Therefore, the identification of the mechanisms regulating cancer stem cell proliferation, survival and dissemination is relevant to block tumor growth and metastasis.

The researchers of Aging and Cancer group generated mouse models that allow studying the cancer stem cell function and regulation during skin cancer progression, from early stages, when these tumors conserve epithelial differentiation features and reduced metastasis capability, to highly undifferentiated and aggressive carcinomas, which present an enhanced metastasis capability. Their results demonstrated that in advanced carcinomas, the frequency of cancer stem cells dramatically increases and these cells strongly induce the epithelial-to-mesenchymal transition program, which enable tumor cell dissemination to distant tissues. Furthermore, regulatory mechanisms that control cancer stem cell proliferation, survival and dissemination change at the late stages of tumor progression. Indeed, whereas EGFR pathway promotes the growth of early carcinomas, this pathway is attenuated in advanced tumors, and FGFR1 and PDGFRa signaling pathways are instead activated to promote aggressive tumor growth and metastasis, respectively. In addition, the analysis of patient samples, carried out in collaboration with Plastic Surgery Service and Pathology Unit of the Hospital de Bellvitge (IDIBELL), showed that, similarly to that reported in mouse carcinomas, recurrent human squamous cell carcinomas exhibit a strong induction of the epithelial-to-mesenchymal transition program and PDGFR and FGFR1 signaling.

Given that, some pharmacological inhibitors that block the activity of these receptors are currently available these findings offer the basis for new targeted therapies to the treatment of advanced skin carcinomas, which may improve the health quality and survival of patients.

Reference of the article:

Cancer stem-like cells act at via distinct signaling pathways in promoting late stages of malignant progression.
da Silva-Diz V, Simón-Extremera P*, Bernat-Peguera A*, de Sostoa J, Urpí M, Penin RM, Pérez Sidelnikova D, Bermejo O, Viñals JM, Rodolosse A, Gonzalez-Suarez E, Gómez Moruno A, Pujana MA, Esteller M, Villanueva A, Viñals F, Muñoz P.
Cancer Res. 2015 Dec 30. pii: canres.1631.2015. [Epub ahead of print].

* contributed equally

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