The Secreted Protein C10orf118 Is a New Regulator of Hyaluronan Synthesis Involved in Tumour-Stroma Cross-Talk

Interaction between cancer cells and their microenvironment is central in defining the fate of cancer development. Tumour cells secrete signals (cytokines, chemokines, growth factors) that modify the surrounding area, while the niche supplies structures and activities necessary for tumour maintenanc...

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Main Authors: Ilaria Caon, Maria Luisa D’Angelo, Barbara Bartolini, Elena Caravà, Arianna Parnigoni, Flavia Contino, Patrizia Cancemi, Paola Moretto, Nikos K. Karamanos, Alberto Passi, Davide Vigetti, Evgenia Karousou, Manuela Viola
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/13/5/1105
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author Ilaria Caon
Maria Luisa D’Angelo
Barbara Bartolini
Elena Caravà
Arianna Parnigoni
Flavia Contino
Patrizia Cancemi
Paola Moretto
Nikos K. Karamanos
Alberto Passi
Davide Vigetti
Evgenia Karousou
Manuela Viola
author_facet Ilaria Caon
Maria Luisa D’Angelo
Barbara Bartolini
Elena Caravà
Arianna Parnigoni
Flavia Contino
Patrizia Cancemi
Paola Moretto
Nikos K. Karamanos
Alberto Passi
Davide Vigetti
Evgenia Karousou
Manuela Viola
author_sort Ilaria Caon
collection DOAJ
description Interaction between cancer cells and their microenvironment is central in defining the fate of cancer development. Tumour cells secrete signals (cytokines, chemokines, growth factors) that modify the surrounding area, while the niche supplies structures and activities necessary for tumour maintenance and growth. Hyaluronan (HA) is a glycosaminoglycan that constitute cancer cell niche and is known to influence tumour functions such as proliferation, migration and neoangiogenesis. The knowledge of the factors regulating HA synthesis and size is crucial in understanding the mechanisms sustaining tumour development. Here we show that a yet uncharacterized protein secreted by breast tumour cell lines, named c10orf118 (accession number NM_018017 in NCBI/BLAST, and Q7z3E2 according to the Uniprot identifier), with a predicted length of 898 amino acids, can induce the secretion of HA by stromal fibroblasts through the up-regulation of the hyaluronan synthase 2 gene (HAS2). Intracellularly, this protein is localized in the Golgi apparatus with a possible role in vesicle maturation and transport. The expression of c10orf118 was verified in breast cancer patient specimens and was found to be associated with the presence of estrogen receptor that characterizes a good patient survival. We suggest c10orf118 as a new player that influences the HA amount in breast cancer microenvironment and is associated with low aggressiveness of cancer.
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spelling doaj.art-006b372428064fda9412bb8410bb85982023-12-03T12:35:44ZengMDPI AGCancers2072-66942021-03-01135110510.3390/cancers13051105The Secreted Protein C10orf118 Is a New Regulator of Hyaluronan Synthesis Involved in Tumour-Stroma Cross-TalkIlaria Caon0Maria Luisa D’Angelo1Barbara Bartolini2Elena Caravà3Arianna Parnigoni4Flavia Contino5Patrizia Cancemi6Paola Moretto7Nikos K. Karamanos8Alberto Passi9Davide Vigetti10Evgenia Karousou11Manuela Viola12Department of Medicine and Surgery, University of Insubria, Via J.H. Dunant 5, 21100 Varese, ItalyDepartment of Medicine and Surgery, University of Insubria, Via J.H. Dunant 5, 21100 Varese, ItalyDepartment of Medicine and Surgery, University of Insubria, Via J.H. Dunant 5, 21100 Varese, ItalyDepartment of Medicine and Surgery, University of Insubria, Via J.H. Dunant 5, 21100 Varese, ItalyDepartment of Medicine and Surgery, University of Insubria, Via J.H. Dunant 5, 21100 Varese, ItalyDepartment of Biological Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90128 Palermo, ItalyDepartment of Biological Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90128 Palermo, ItalyDepartment of Medicine and Surgery, University of Insubria, Via J.H. Dunant 5, 21100 Varese, ItalyBiochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26110 Patras, GreeceDepartment of Medicine and Surgery, University of Insubria, Via J.H. Dunant 5, 21100 Varese, ItalyDepartment of Medicine and Surgery, University of Insubria, Via J.H. Dunant 5, 21100 Varese, ItalyDepartment of Medicine and Surgery, University of Insubria, Via J.H. Dunant 5, 21100 Varese, ItalyDepartment of Medicine and Surgery, University of Insubria, Via J.H. Dunant 5, 21100 Varese, ItalyInteraction between cancer cells and their microenvironment is central in defining the fate of cancer development. Tumour cells secrete signals (cytokines, chemokines, growth factors) that modify the surrounding area, while the niche supplies structures and activities necessary for tumour maintenance and growth. Hyaluronan (HA) is a glycosaminoglycan that constitute cancer cell niche and is known to influence tumour functions such as proliferation, migration and neoangiogenesis. The knowledge of the factors regulating HA synthesis and size is crucial in understanding the mechanisms sustaining tumour development. Here we show that a yet uncharacterized protein secreted by breast tumour cell lines, named c10orf118 (accession number NM_018017 in NCBI/BLAST, and Q7z3E2 according to the Uniprot identifier), with a predicted length of 898 amino acids, can induce the secretion of HA by stromal fibroblasts through the up-regulation of the hyaluronan synthase 2 gene (HAS2). Intracellularly, this protein is localized in the Golgi apparatus with a possible role in vesicle maturation and transport. The expression of c10orf118 was verified in breast cancer patient specimens and was found to be associated with the presence of estrogen receptor that characterizes a good patient survival. We suggest c10orf118 as a new player that influences the HA amount in breast cancer microenvironment and is associated with low aggressiveness of cancer.https://www.mdpi.com/2072-6694/13/5/1105hyaluronanhyaluronan synthase 2breast cancerMCF-7MDA-MB-231estrogen receptor
spellingShingle Ilaria Caon
Maria Luisa D’Angelo
Barbara Bartolini
Elena Caravà
Arianna Parnigoni
Flavia Contino
Patrizia Cancemi
Paola Moretto
Nikos K. Karamanos
Alberto Passi
Davide Vigetti
Evgenia Karousou
Manuela Viola
The Secreted Protein C10orf118 Is a New Regulator of Hyaluronan Synthesis Involved in Tumour-Stroma Cross-Talk
Cancers
hyaluronan
hyaluronan synthase 2
breast cancer
MCF-7
MDA-MB-231
estrogen receptor
title The Secreted Protein C10orf118 Is a New Regulator of Hyaluronan Synthesis Involved in Tumour-Stroma Cross-Talk
title_full The Secreted Protein C10orf118 Is a New Regulator of Hyaluronan Synthesis Involved in Tumour-Stroma Cross-Talk
title_fullStr The Secreted Protein C10orf118 Is a New Regulator of Hyaluronan Synthesis Involved in Tumour-Stroma Cross-Talk
title_full_unstemmed The Secreted Protein C10orf118 Is a New Regulator of Hyaluronan Synthesis Involved in Tumour-Stroma Cross-Talk
title_short The Secreted Protein C10orf118 Is a New Regulator of Hyaluronan Synthesis Involved in Tumour-Stroma Cross-Talk
title_sort secreted protein c10orf118 is a new regulator of hyaluronan synthesis involved in tumour stroma cross talk
topic hyaluronan
hyaluronan synthase 2
breast cancer
MCF-7
MDA-MB-231
estrogen receptor
url https://www.mdpi.com/2072-6694/13/5/1105
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