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COL11A1/(pro)collagen 11A1 expression is a remarkable biomarker of human invasive carcinoma-associated stromal cells and carcinoma progression

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Tumor Biology

Abstract

The COL11A1 human gene codes for the α1 chain of procollagen 11A1 and mature collagen 11A1, an extracellular minor fibrillar collagen. Under regular conditions, this gene and its derived products are mainly expressed by chondrocytes and mesenchymal stem cells as well as osteoblasts. Normal epithelial cells and quiescent fibroblasts from diverse locations do not express them. Mesenchyme-derived tumors and related conditions, such as scleroderma and keloids, are positive for COL11A1/(pro)collagen 11A1 expression, as well as high-grade human gliomas/glioblastomas. This expression is almost absent in benign pathological processes such as breast hyperplasia, sclerosing adenosis, idiopathic pulmonary fibrosis, cirrhosis, pancreatitis, diverticulitis, and inflammatory bowel disease. By contrast, COL11A1/(pro)collagen 11A1 is highly expressed by activated stromal cells of the desmoplastic reaction of different human invasive carcinomas, and this expression is correlated with carcinoma aggressiveness and progression, and lymph node metastasis. COL11A1 upregulation has been shown to be associated to TGF-β1, Wnt, and Hh signaling pathways, which are especially active in cancer-associated stromal cells. At the front of invasive carcinomas, neoplastic epithelial cells, putatively undergoing epithelial-to-mesenchymal transition, and carcinoma-derived cells with highly metastatic capabilities, can express COL11A1. Thus, in established metastases, the expression of COL11A1/(pro)collagen 11A1 could rely on both the metastatic epithelial cells and/or the accompanying activated stromal cells. COL11A1/(pro)collagen 11A1 expression is a remarkable biomarker of human carcinoma-associated stromal cells and carcinoma progression.

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Acknowledgments

The authors thank Inti Zlobec for the critical reading of the manuscript and helpful comments. This work was co-financed by European Union ERDF Funds; by the INNPACTO-ONCOPAN IPT-010000-2010-31 Project; by the FISS-09-PS09/01911 Project, Ministry of Science and Innovation, Spain; by the FC-11-PC10-23, FICYT Project, Axe 1 of the 2007–2013 ERDF Operational Framework Programme of the Principality of Asturias, Spain; and by Oncomatrix, S.L. Derio, Spain.

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Author notes

  1. José A. Galván

    Present address: Translational Research Unit (TRU), Institute of Pathology, University of Bern, Bern, Switzerland

Authors and Affiliations

  1. Surgery Department, School of Medicine and Health Sciences, University of Oviedo, 33006, Oviedo, Spain

    Fernando Vázquez-Villa, José A. Galván, Jorge García-Martínez & Luis Barneo-Serra

  2. Oncology University Institute of the Principality of Asturias (IUOPA), 33006, Oviedo, Spain

    Fernando Vázquez-Villa, Marcos García-Ocaña, José A. Galván, Jorge García-Martínez, Carmen García-Pravia, Luis Barneo-Serra & Juan R. de los Toyos

  3. Preparative Biotechnology Unit, Technical-Scientific Services, University of Oviedo, 33006, Oviedo, Spain

    Marcos García-Ocaña

  4. Pathological Anatomy Service, Asturias Central University Hospital (HUCA), 33006, Oviedo, Spain

    Carmen García-Pravia, Primitiva Menéndez-Rodríguez & Carmen González-del Rey

  5. Immunology Department, School of Medicine and Health Sciences, University of Oviedo, 33006, Oviedo, Spain

    Juan R. de los Toyos

  6. Área de Inmunología, Facultad de Medicina y Ciencias de la Salud, Universidad de Oviedo, c/ Julián Clavería s/n, 33006, Oviedo, Spain

    Juan R. de los Toyos

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  1. Fernando Vázquez-Villa
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Correspondence to Juan R. de los Toyos.

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Vázquez-Villa, F., García-Ocaña, M., Galván, J.A. et al. COL11A1/(pro)collagen 11A1 expression is a remarkable biomarker of human invasive carcinoma-associated stromal cells and carcinoma progression. Tumor Biol. 36, 2213–2222 (2015). https://doi.org/10.1007/s13277-015-3295-4

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