University of Oulu

Martínez-Nieto, G.; Heljasvaara, R.; Heikkinen, A.; Kaski, H.-K.; Devarajan, R.; Rinne, O.; Henriksson, C.; Thomson, E.; von Hertzen, C.; Miinalainen, I.; Ruotsalainen, H.; Pihlajaniemi, T.; Karppinen, S.-M. Deletion of Col15a1 Modulates the Tumour Extracellular Matrix and Leads to Increased Tumour Growth in the MMTV-PyMT Mouse Mammary Carcinoma Model. Int. J. Mol. Sci. 2021, 22, 9978. https://doi.org/10.3390/ijms22189978

Deletion of Col15a1 modulates the tumour extracellular matrix and leads to increased tumour growth in the MMTV-PyMT mouse mammary carcinoma model

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Author: Martínez-Nieto, Guillermo1; Heljasvaara, Ritva1; Heikkinen, Anne1,2;
Organizations: 1Oulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu, 90220 Oulu, Finland
2Biocenter Oulu, University of Oulu, 90220 Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 8.3 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2021102852807
Language: English
Published: Multidisciplinary Digital Publishing Institute, 2021
Publish Date: 2021-10-28
Description:

Abstract

Basement membrane (BM) zone-associated collagen XV (ColXV) has been shown to suppress the malignancy of tumour cells, and its restin domain can inhibit angiogenesis. In human breast cancer, as well as in many other human carcinomas, ColXV is lost from the epithelial BM zone prior to tumour invasion. Here, we addressed the roles of ColXV in breast carcinogenesis using the transgenic MMTV-PyMT mouse mammary carcinoma model. We show here for the first time that the inactivation of Col15a1 in mice leads to changes in the fibrillar tumour matrix and to increased mammary tumour growth. ColXV is expressed by myoepithelial and endothelial cells in mammary tumours and is lost from the ductal BM along with the loss of the myoepithelial layer during cancer progression while persisting in blood vessels and capillaries, even in invasive tumours. However, despite the absence of anti-angiogenic restin domain, neovascularisation was reduced rather than increased in the ColXV-deficient mammary tumours compared to controls. We also show that, in robust tumour cell transplantation models or in a chemical-induced fibrosarcoma model, the inactivation of Col15a1 does not affect tumour growth or angiogenesis. In conclusion, our results support the proposed tumour suppressor function of ColXV in mammary carcinogenesis and reveal diverse roles of this collagen in different cancer types

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Series: International journal of molecular sciences
ISSN: 1661-6596
ISSN-E: 1422-0067
ISSN-L: 1661-6596
Volume: 22
Issue: 18
Article number: 9978
DOI: 10.3390/ijms22189978
OADOI: https://oadoi.org/10.3390/ijms22189978
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Subjects:
Funding: The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme FP7/2007-2013/under REA grant agreement no. 316610, and from the Academy of Finland (grants 308867 and 284065 for TP, 259872 for SMK, and 128259 for RH), the Cancer Foundation Finland (grants 190147 and 170138), the Sigrid Jusélius Foundation, the Jane and Aatos Erkko Foundation, the Emil Aaltonen Foundation and the Finnish Cultural Foundation.
Academy of Finland Grant Number: 308867
284065
259872
128259
Detailed Information: 308867 (Academy of Finland Funding decision)
284065 (Academy of Finland Funding decision)
259872 (Academy of Finland Funding decision)
128259 (Academy of Finland Funding decision)
Copyright information: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
  https://creativecommons.org/licenses/by/4.0/