Collagen molecular phenotypic switch between non-neoplastic and neoplastic canine mammary tissues

Abstract In spite of major advances over the past several decades in diagnosis and treatment, breast cancer remains a global cause of morbidity and premature death for both human and veterinary patients. Due to multiple shared clinicopathological features, dogs provide an excellent model of human br...

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Autores principales:	Masahiko Terajima, Yuki Taga, Becky K. Brisson, Amy C. Durham, Kotaro Sato, Katsuhiro Uzawa, Tomoaki Saito, Shunji Hattori, Karin U. Sørenmo, Mitsuo Yamauchi, Susan W. Volk
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a69f3270876347f99c52b1f4d5b5dcfe
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spelling	oai:doaj.org-article:a69f3270876347f99c52b1f4d5b5dcfe2021-12-02T16:45:06ZCollagen molecular phenotypic switch between non-neoplastic and neoplastic canine mammary tissues10.1038/s41598-021-87380-y2045-2322https://doaj.org/article/a69f3270876347f99c52b1f4d5b5dcfe2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87380-yhttps://doaj.org/toc/2045-2322Abstract In spite of major advances over the past several decades in diagnosis and treatment, breast cancer remains a global cause of morbidity and premature death for both human and veterinary patients. Due to multiple shared clinicopathological features, dogs provide an excellent model of human breast cancer, thus, a comparative oncology approach may advance our understanding of breast cancer biology and improve patient outcomes. Despite an increasing awareness of the critical role of fibrillar collagens in breast cancer biology, tumor-permissive collagen features are still ill-defined. Here, we characterize the molecular and morphological phenotypes of type I collagen in canine mammary gland tumors. Canine mammary carcinoma samples contained longer collagen fibers as well as a greater population of wider fibers compared to non-neoplastic and adenoma samples. Furthermore, the total number of collagen cross-links enriched in the stable hydroxylysine-aldehyde derived cross-links was significantly increased in neoplastic mammary gland samples compared to non-neoplastic mammary gland tissue. The mass spectrometric analyses of type I collagen revealed that in malignant mammary tumor samples, lysine residues, in particular those in the telopeptides, were markedly over-hydroxylated in comparison to non-neoplastic mammary tissue. The extent of glycosylation of hydroxylysine residues was comparable among the groups. Consistent with these data, expression levels of genes encoding lysyl hydroxylase 2 (LH2) and its molecular chaperone FK506-binding protein 65 were both significantly increased in neoplastic samples. These alterations likely lead to an increase in the LH2-mediated stable collagen cross-links in mammary carcinoma that may promote tumor cell metastasis in these patients.Masahiko TerajimaYuki TagaBecky K. BrissonAmy C. DurhamKotaro SatoKatsuhiro UzawaTomoaki SaitoShunji HattoriKarin U. SørenmoMitsuo YamauchiSusan W. VolkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Masahiko Terajima Yuki Taga Becky K. Brisson Amy C. Durham Kotaro Sato Katsuhiro Uzawa Tomoaki Saito Shunji Hattori Karin U. Sørenmo Mitsuo Yamauchi Susan W. Volk Collagen molecular phenotypic switch between non-neoplastic and neoplastic canine mammary tissues
description	Abstract In spite of major advances over the past several decades in diagnosis and treatment, breast cancer remains a global cause of morbidity and premature death for both human and veterinary patients. Due to multiple shared clinicopathological features, dogs provide an excellent model of human breast cancer, thus, a comparative oncology approach may advance our understanding of breast cancer biology and improve patient outcomes. Despite an increasing awareness of the critical role of fibrillar collagens in breast cancer biology, tumor-permissive collagen features are still ill-defined. Here, we characterize the molecular and morphological phenotypes of type I collagen in canine mammary gland tumors. Canine mammary carcinoma samples contained longer collagen fibers as well as a greater population of wider fibers compared to non-neoplastic and adenoma samples. Furthermore, the total number of collagen cross-links enriched in the stable hydroxylysine-aldehyde derived cross-links was significantly increased in neoplastic mammary gland samples compared to non-neoplastic mammary gland tissue. The mass spectrometric analyses of type I collagen revealed that in malignant mammary tumor samples, lysine residues, in particular those in the telopeptides, were markedly over-hydroxylated in comparison to non-neoplastic mammary tissue. The extent of glycosylation of hydroxylysine residues was comparable among the groups. Consistent with these data, expression levels of genes encoding lysyl hydroxylase 2 (LH2) and its molecular chaperone FK506-binding protein 65 were both significantly increased in neoplastic samples. These alterations likely lead to an increase in the LH2-mediated stable collagen cross-links in mammary carcinoma that may promote tumor cell metastasis in these patients.
format	article
author	Masahiko Terajima Yuki Taga Becky K. Brisson Amy C. Durham Kotaro Sato Katsuhiro Uzawa Tomoaki Saito Shunji Hattori Karin U. Sørenmo Mitsuo Yamauchi Susan W. Volk
author_facet	Masahiko Terajima Yuki Taga Becky K. Brisson Amy C. Durham Kotaro Sato Katsuhiro Uzawa Tomoaki Saito Shunji Hattori Karin U. Sørenmo Mitsuo Yamauchi Susan W. Volk
author_sort	Masahiko Terajima
title	Collagen molecular phenotypic switch between non-neoplastic and neoplastic canine mammary tissues
title_short	Collagen molecular phenotypic switch between non-neoplastic and neoplastic canine mammary tissues
title_full	Collagen molecular phenotypic switch between non-neoplastic and neoplastic canine mammary tissues
title_fullStr	Collagen molecular phenotypic switch between non-neoplastic and neoplastic canine mammary tissues
title_full_unstemmed	Collagen molecular phenotypic switch between non-neoplastic and neoplastic canine mammary tissues
title_sort	collagen molecular phenotypic switch between non-neoplastic and neoplastic canine mammary tissues
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a69f3270876347f99c52b1f4d5b5dcfe
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Collagen molecular phenotypic switch between non-neoplastic and neoplastic canine mammary tissues

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