Abstract
Simple SummaryThe 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 of COL11A1. In contrast, nonhierarchical clustering revealed a more specific gene expression pattern for AdCy, characterized by overexpression of COL27A1. 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 (including COL11A1) and four glycoproteins from MuEp and SaDu suggested a common ECM alteration. Conversely, AdCy and MuEp displayed a distinct overexpression of COL27A1 and LAMB3, 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 of COL27A1, 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.
Highlights
The extracellular matrix (ECM) is an integral part of the tumour microenvironment (TME)
11 patients with adenoid cystic (AdCy), 14 with MuEp and 9 with salivary duct carcinomas (SaDu) were enrolled in the study
The ECM of carcinomas is vital for cancer progression and therapy resistance
Summary
The extracellular matrix (ECM) is an integral part of the tumour microenvironment (TME). All matrix proteins have recently been termed “the matrisome” [3] This organ- and context-specific network [4] is gradually altered throughout tumour initiation [5,6,7,8], progression and metastasis [9,10] as it provides a niche for tumour cell survival [4,11]. High ratios of the resulting peritumoural stroma have been associated with an adverse outcome in a multitude of primaries [14] This effect can be partially attributed to ECM-stiffening through collagen cross-linking and ECM-deposition, which leads to augmented invasive capacities [15], epithelial-to-mesenchymal transition [16] and the reduced bioavailability of antineoplastic agents [17,18]. Transcriptomic studies have recently demonstrated that certain ECM-signatures are prognostic of patient survival in several other primaries [19,20,21,22], the ECM composition of salivary gland carcinomas (SGC) remains largely unknown [23,24,25]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
