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Analysis of institutional authors

Gallego-Rentero MAuthorMascaraque MAuthorCarrasco ECorresponding AuthorJuarranz ACorresponding Author

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Tgfβ1 secreted by cancer-associated fibroblasts as an inductor of resistance to photodynamic therapy in squamous cell carcinoma cells

Publicated to:Cancers. 13 (22): 5613- - 2021-11-01 13(22), DOI: 10.3390/cancers13225613

Authors: Gallego-Rentero, Maria; Gutierrez-Perez, Maria; Fernandez-Guarino, Montserrat; Mascaraque, Marta; Portillo-Esnaola, Mikel; Gilaberte, Yolanda; Carrasco, Elisa; Juarranz, Angeles

Affiliations

Hosp Miguel Servet, Serv Dermatol, Zaragoza 50009, Spain - Author
Hosp Ramon & Cajal, Dermatol Serv, Madrid 28034, Spain - Author
Hospital Miguel Servet - Author
Instituto Ramón y Cajal de Investigación Sanitaria , Hospital Ramon y Cajal - Author
Instituto Ramón y Cajal de Investigación Sanitaria , Universidad Autónoma de Madrid - Author
IRYCIS, Inst Ramon y Cajal Invest Sanitaria, Madrid 28034, Spain - Author
Univ Autonoma Madrid, Dept Biol, Madrid 28049, Spain - Author
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Abstract

As an important component of tumor microenvironment, cancer-associated fibroblasts (CAFs) have lately gained prominence owing to their crucial role in the resistance to therapies. Photodynamic therapy (PDT) stands out as a successful therapeutic strategy to treat cutaneous squamous cell carcinoma. In this study, we demonstrate that the transforming growth factor β1 (TGFβ1) cytokine secreted by CAFs isolated from patients with SCC can drive resistance to PDT in epithelial SCC cells. To this end, CAFs obtained from patients with in situ cSCC were firstly characterized based on the expression levels of paramount markers as well as the levels of TGFβ1 secreted to the extracellular environment. On a step forward, two established human cSCC cell lines (A431 and SCC13) were pre-treated with conditioned medium obtained from the selected CAF cultures. The CAF-derived conditioned medium effectively induced resistance to PDT in A431 cells through a reduction in the cell proliferation rate. This resistance effect was recapitulated by treating with recombinant TGFβ1 and abolished by using the SB525334 TGFβ1 receptor inhibitor, providing robust evidence of the role of TGFβ1 secreted by CAFs in the development of resistance to PDT in this cell line. Conversely, higher levels of recombinant TGFβ1 were needed to reduce cell proliferation in SCC13 cells, and no induction of resistance to PDT was observed in this cell line in response to CAF-derived conditioned medium. Interestingly, we probed that the comparatively higher intrinsic resistance to PDT of SCC13 cells was mediated by the elevated levels of TGFβ1 secreted by this cell line. Our results point at this feature as a promising biomarker to predict both the suitability of PDT and the chances to optimize the treatment by targeting CAF-derived TGFβ1 in the road to a more personalized treatment of particular cSCC tumors.

Keywords

a431basalcancer-associated fibroblastsdiagnosisepidemiologyexpressionfibroblastsgrowthinhibitionpathwaysphotodynamic therapyresistancescc13skinsquamous cell carcinomatgf betatgf?tgfβtumor microenvironmentA431Cancer-associated fibroblastsFibroblastsPhotodynamic therapyResistanceScc13SkinSquamous cell carcinomaTgf betaTgf-betaTgfβTumor microenvironment

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Cancers due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2021, it was in position 60/245, thus managing to position itself as a Q1 (Primer Cuartil), in the category Oncology.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.73. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 1.68 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 4.92 (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-01, the following number of citations:

  • WoS: 19
  • Scopus: 20
  • Europe PMC: 7

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-01:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 24.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 24 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 1.
  • The number of mentions on the social network X (formerly Twitter): 1 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: https://repositorio.uam.es/handle/10486/703566

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (GALLEGO RENTERO, MARIA) and Last Author (JUARRANZ DE LA FUENTE, ANGELES).

the authors responsible for correspondence tasks have been CARRASCO CERRO, ELISA and JUARRANZ DE LA FUENTE, ANGELES.