Tenascin-C increases lung metastasis by impacting blood vessel invasions

Sun, Zhen; Velázquez-Quesada, Inés; Murdamoothoo, Devadarssen; Ahowesso, Constance; Yılmaz, Alev; Spenlé, Caroline; Avérous, Gerlinde; Erne, William; Oberndorfer, Felicitas; Oszwald, André; Kain, Renate; Bourdon, Catherine; Mangin, P; Deligne, Claire; Midwood, Kim S.; Abou-Faycal, Chérine; Lefèbvre, Olivier; Klein, Albrecht; Heyden, Michael van der; Chenard, Marie–Pierre; Christofori, Gerhard; Mathelin, Carole; Loustau, Thomas; Hussenet, Thomas; Orend, Gertraud

doi:10.1016/j.matbio.2019.07.001

Cited by 52 publications

(57 citation statements)

References 61 publications

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“…In summary, we revealed an overexpression of ECM components, which are associated with enhanced migratory capacities of tumour cells ( TNC [ 76 , 77 ], FN1 [ 78 ]), resistance to chemotherapy ( COL11A1 [ 43 , 75 ], SPP1 [ 79 ]) and adverse outcome ( COL11A1 [ 42 ], TNC [ 80 ], FN1 [ 78 ]) in other primaries. The functional role of these molecules and their potential as therapeutic targets are currently under intense investigation [ 65 , 66 , 75 , 79 , 81 , 82 ].…”

Section: Discussionmentioning

confidence: 99%

Expression Profiling of Extracellular Matrix Genes Reveals Global and Entity-Specific Characteristics in Adenoid Cystic, Mucoepidermoid and Salivary Duct Carcinomas

Arolt

Meyer

Hoffmann

et al. 2020

Cancers

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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.

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Section: Discussionmentioning

confidence: 99%

Expression Profiling of Extracellular Matrix Genes Reveals Global and Entity-Specific Characteristics in Adenoid Cystic, Mucoepidermoid and Salivary Duct Carcinomas

Arolt

Meyer

Hoffmann

et al. 2020

Cancers

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“…1C). TN-C is frequently observed to be expressed along the border of matrix tracks in skin (200), pulmonary (201), colorectal (202) and breast (203) cancers. In fact, TN-C assembles into matrix tracks with ECM molecules such as fibronectin, laminins and several collagens (200,204), which are also linked to metastatic potential (200,205,206).…”

Section: Mcp Influence On the Metastatic Nichementioning

confidence: 99%

The Matrix Revolution: Matricellular Proteins and Restructuring of the Cancer Microenvironment

et al. 2020

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The extracellular matrix (ECM) surrounding cells is indispensable for regulating their behavior. The dynamics of ECM signaling are tightly controlled throughout growth and development. During tissue remodeling, matricellular proteins (MCPs) are secreted into the ECM. These factors do not serve classical structural roles, but rather regulate matrix proteins and cell-matrix interactions to influence normal cellular functions. In the tumor microenvironment, it is becoming increasingly clear that aberrantly expressed MCPs can support multiple hallmarks of carcinogenesis by interacting with various cellular components that are coupled to an array of downstream signals. Moreover, MCPs also reorganize the biomechanical properties of the ECM to accommodate metastasis and tumor colonization. This realization is stimulating new research on MCPs as reliable and accessible biomarkers in cancer, as well as effective and selective therapeutic targets. Research.

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“…4e-h). Given that stromal-derived TNC increases metastasis by reducing apoptosis and inducing the cellular plasticity of cancer cells 25 , we then investigated whether TNCknockdown induced apoptosis in glioma cell. As expected, TNC-knockdown increased Annexin V positive cells in both U251 and A172 glioma cells (*p < 0.05, **p < 0.01; Fig.…”

Section: Tnc Knockdown Attenuated Vm Formation In Vitro and In Vivomentioning

confidence: 99%

Tenascin-c mediated vasculogenic mimicry formation via regulation of MMP2/MMP9 in glioma

Cai

Wang

et al. 2019

Cell Death Dis

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Vasculogenic mimicry (VM), the formation of vessel-like structures by highly invasive tumor cells, has been considered one of several mechanisms responsible for the failure of anti-angiogenesis therapy in glioma patients. Therefore, inhibiting VM formation might be an effective therapeutic method to antagonize the angiogenesis resistance. This study aimed to show that an extracellular protein called Tenascin-c (TNC) is involved in VM formation and that TNC knockdown inhibits VM in glioma. TNC was upregulated with an increase in glioma grade. TNC and VM formation are potential independent predictors of survival of glioma patients. TNC upregulation was correlated with VM formation, and exogenous TNC stimulated VM formation. Furthermore, TNC knockdown significantly suppressed VM formation and proliferation in glioma cells in vitro and in vivo, with a reduction in cellular invasiveness and migration. Mechanistically, TNC knockdown decreased Akt phosphorylation at Ser 473 and Thr 308 and subsequently downregulated matrix metalloproteinase 2 and 9, both of which are important proteins associated with VM formation and migration. Our results indicate that TNC plays an important role in VM formation in glioma, suggesting that TNC is a potential therapeutic target for anti-angiogenesis therapy for glioma.

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Tenascin-C increases lung metastasis by impacting blood vessel invasions

Cited by 52 publications

References 61 publications

Expression Profiling of Extracellular Matrix Genes Reveals Global and Entity-Specific Characteristics in Adenoid Cystic, Mucoepidermoid and Salivary Duct Carcinomas

Expression Profiling of Extracellular Matrix Genes Reveals Global and Entity-Specific Characteristics in Adenoid Cystic, Mucoepidermoid and Salivary Duct Carcinomas

The Matrix Revolution: Matricellular Proteins and Restructuring of the Cancer Microenvironment

Tenascin-c mediated vasculogenic mimicry formation via regulation of MMP2/MMP9 in glioma

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