Universität zu Köln

Arolt, Christoph, Meyer, Moritz, Hoffmann, Franziska ORCID: 0000-0002-6872-924X, Wagener-Ryczek, Svenja, Schwarz, David, Nachtsheim, Lisa, Beutner, Dirk, Odenthal, Margarete ORCID: 0000-0002-2424-0960, Guntinas-Lichius, Orlando ORCID: 0000-0001-9671-0784, Buettner, Reinhard, von Eggeling, Ferdinand ORCID: 0000-0002-8062-6999, Klussmann, Jens Peter and Quaas, Alexander (2020). Expression Profiling of Extracellular Matrix Genes Reveals Global and Entity-Specific Characteristics in Adenoid Cystic, Mucoepidermoid and Salivary Duct Carcinomas. Cancers, 12 (9). BASEL: MDPI. ISSN 2072-6694

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Abstract

Simple Summary The extracellular matrix (ECM), an important factor in tumour metastasis and therapy resistance, has not been studied in salivary gland carcinomas (SGC), so far. In this retrospective study, we profiled the RNA expression of 28 ECM-related genes in 11 adenoid cystic (AdCy), 14 mucoepidermoid (MuEp) and 9 salivary duct carcinomas (SaDu). Also, we validated our results in a multimodal approach. MuEp and SaDu shared a common gene signature involving an overexpression ofCOL11A1. In contrast, nonhierarchical clustering revealed a more specific gene expression pattern for AdCy, characterized by overexpression ofCOL27A1. In situ studies at RNA level indicated that in AdCy, ECM production results from tumour cells and not from cancer-associated fibroblasts as is the case in MuEp and SaDu. For the first time, we characterized the ECM composition in SGC and identified several differentially expressed genes, which are potential therapeutic targets. The composition of the extracellular matrix (ECM) plays a pivotal role in tumour initiation, metastasis and therapy resistance. Until now, the ECM composition of salivary gland carcinomas (SGC) has not been studied. We quantitatively analysed the mRNA of 28 ECM-related genes of 34 adenoid cystic (AdCy;n= 11), mucoepidermoid (MuEp;n= 14) and salivary duct carcinomas (SaDu;n= 9). An incremental overexpression of six collagens (includingCOL11A1) and four glycoproteins from MuEp and SaDu suggested a common ECM alteration. Conversely, AdCy and MuEp displayed a distinct overexpression ofCOL27A1andLAMB3, respectively. Nonhierarchical clustering and principal component analysis revealed a more specific pattern for AdCy with low expression of the common gene signature. In situ studies at the RNA and protein level confirmed these results and indicated that, in contrast to MuEp and SaDu, ECM production in AdCy results from tumour cells and not from cancer-associated fibroblasts (CAFs). Our findings reveal different modes of ECM production leading to common and distinct RNA signatures in SGC. Of note, an overexpression ofCOL27A1, as in AdCy, has not been linked to any other neoplasm so far. Here, we contribute to the dissection of the ECM composition in SGC and identified a panel of deferentially expressed genes, which could be putative targets for SGC therapy and overcoming therapeutic resistance.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Arolt, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Meyer, Moritz UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoffmann, Franziska UNSPECIFIED orcid.org/0000-0002-6872-924X UNSPECIFIED Wagener-Ryczek, Svenja UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwarz, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Nachtsheim, Lisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Beutner, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED Odenthal, Margarete UNSPECIFIED orcid.org/0000-0002-2424-0960 UNSPECIFIED Guntinas-Lichius, Orlando UNSPECIFIED orcid.org/0000-0001-9671-0784 UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED von Eggeling, Ferdinand UNSPECIFIED orcid.org/0000-0002-8062-6999 UNSPECIFIED Klussmann, Jens Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Quaas, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-320270
DOI:	10.3390/cancers12092466
Journal or Publication Title:	Cancers
Volume:	12
Number:	9
Date:	2020
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2072-6694
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CANCER CELLS; TENASCIN-C; STEEL SYNDROME; COLLAGEN; METASTASIS; SIGNATURE; SURVIVAL; MYBL1; OVEREXPRESSION; LAMININ-332 Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/32027