Matrix metalloproteinase expression in high grade soft tissue sarcomas

Alford, Stephanie H.; Vrana, Michael S.; Waite, Lindsay L.; Heim-Hall, Josefine; Sylvia, V. L.; Williams, Ronald P.

doi:10.3892/or.18.6.1529

Cited by 6 publications

(8 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, CD147 expression has already been previously studied in a cohort of high grade soft tissue sarcomas, however, with no significant prognostic value [33]. In the present study, as the cohort also included low grade tumors, CD147 was significantly associated with high grade tumors.…”

Section: Discussionmentioning

confidence: 47%

Characterization of monocarboxylate transporters (MCTs) expression in soft tissue sarcomas: distinct prognostic impact of MCT1 sub-cellular localization

et al. 2014

View full text Add to dashboard Cite

BackgroundSoft tissue sarcomas (STSs) are a group of neoplasms, which, despite current therapeutic advances, still confer a poor outcome to half of the patients. As other solid tumors, STSs exhibit high glucose consumption rates, associated with worse prognosis and therapeutic response. As highly glycolytic tumors, we hypothesized that sarcomas should present an increased expression of lactate transporters (MCTs).MethodsImmunohistochemical expression of MCT1, MCT2, MCT4 and CD147 was assessed in a series of 86 STSs and the expression profiles were associated with patients’ clinical-pathological parameters.ResultsMCT1, MCT4 and CD147 were mainly observed in the plasma membrane of cancer cells (around 60% for MCTs and 40% for CD147), while MCT2 was conspicuously found in the cytoplasm (94.2%). Importantly, we observed MCT1 nuclear expression (32.6%). MCT1 and MCT4, alone or co-expressed with CD147 in the plasma membrane, were associated with poor prognostic variables including high tumor grade, disease progression and shorter overall survival. Conversely, we found MCT1 nuclear expression to be associated with low grade tumors and longer overall survival.ConclusionsThe present work represents the first report of MCTs characterization in STSs. We showed the original finding of MCT1 expression in the nucleus. Importantly, opposite biological roles should be behind the dual sub-cellular localization of MCT1, as plasma membrane expression of MCT1 is associated with worse patients’ prognosis, while nuclear expression is associated with better prognosis.

show abstract

Section: Discussionmentioning

confidence: 47%

Characterization of monocarboxylate transporters (MCTs) expression in soft tissue sarcomas: distinct prognostic impact of MCT1 sub-cellular localization

et al. 2014

View full text Add to dashboard Cite

show abstract

“…The same is true for rs2071888 in TAPBP , a missense mutation. As noted above, several studies have observed over-expression of matrix metalloproteinase genes in GISTs and other soft tissue sarcomas [ 23 - 25 ], though none of the evaluated SNPs have previously been associated with cancer risk.…”

Section: Discussionmentioning

confidence: 99%

“…The present report includes results from the second phase of the study, in which we examined the relationship between these 7 somatic mutation categories and 522 additional candidate SNPs. These SNPs are located on genes that play secondary or less well-understood roles in dioxin response or toxin-metabolizing pathways, as well as SNPs on PDGFRA and 10 matrix metalloproteinase ( MMP ) genes, which are often over-expressed in GISTs and other soft tissue sarcomas and may be linked to tumor invasion and metastasis [ 23 - 25 ]. Based on previous evidence that immune and inflammation-related genes are associated with osteosarcomas and other gastrointestinal tumors [ 26 - 28 ], we also selected certain SNPs from the GeneChip® Human Immune and Inflammation SNP Kit genotyping panel designed by Affymetrix® [ 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

Gastrointestinal stromal tumors: a case-only analysis of single nucleotide polymorphisms and somatic mutations

et al. 2013

View full text Add to dashboard Cite

BackgroundGastrointestinal stromal tumors are rare soft tissue sarcomas that typically develop from mesenchymal cells with acquired gain-in-function mutations in KIT or PDGFRA oncogenes. These somatic mutations have been well-characterized, but little is known about inherited genetic risk factors. Given evidence that certain susceptibility loci and carcinogens are associated with characteristic mutations in other cancers, we hypothesized that these signature KIT or PDGFRA mutations may be similarly fundamental to understanding gastrointestinal stromal tumor etiology. Therefore, we examined associations between 522 single nucleotide polymorphisms and seven KIT or PDGFRA tumor mutations types. Candidate pathways included dioxin response, toxin metabolism, matrix metalloproteinase production, and immune and inflammatory response.MethodsWe estimated odds ratios and 95% confidence intervals for associations between each candidate SNP and tumor mutation type in 279 individuals from a clinical trial of adjuvant imatinib mesylate. We used sequence kernel association tests to look for pathway-level associations.ResultsOne variant, rs1716 on ITGAE, was significantly associated with KIT exon 11 non-codon 557–8 deletions (odds ratio = 2.86, 95% confidence interval: 1.71-4.78) after adjustment for multiple comparisons. Other noteworthy associations included rs3024498 (IL10) and rs1050783 (F13A1) with PDGFRA mutations, rs2071888 (TAPBP) with wild type tumors and several matrix metalloproteinase SNPs with KIT exon 11 codon 557–558 deletions. Several pathways were strongly associated with somatic mutations in PDGFRA, including defense response (p = 0.005) and negative regulation of immune response (p = 0.01).ConclusionsThis exploratory analysis offers novel insights into gastrointestinal stromal tumor etiology and provides a starting point for future studies of genetic and environmental risk factors for the disease.

show abstract

“…The metalloproteinase inhibitor TIMP4 that was found to be the most downregulated gene has previously been associated with efficient tumor suppression in breast cancer cells [45] and its [46], a study that selectively focused on spindle-cell-like lesions could correlate higher MMP and lower TIMP expression to high-grade and malignant tumors [47]. Interestingly, all the genes identified as differentially regulated in the tumors that developed metastasis were downregulated compared to their expression in the tumors that did not seed distant lesions.…”

Section: Discussionmentioning

confidence: 99%

Malignant fibrous histiocytoma—pleomorphic sarcoma, NOS gene expression, histology, and clinical course. A pilot study

Daigeler

Klein-Hitpaß

Stricker

et al. 2009

Langenbecks Arch Surg

View full text Add to dashboard Cite

show abstract

Matrix metalloproteinase expression in high grade soft tissue sarcomas

Cited by 6 publications

References 14 publications

Characterization of monocarboxylate transporters (MCTs) expression in soft tissue sarcomas: distinct prognostic impact of MCT1 sub-cellular localization

Characterization of monocarboxylate transporters (MCTs) expression in soft tissue sarcomas: distinct prognostic impact of MCT1 sub-cellular localization

Gastrointestinal stromal tumors: a case-only analysis of single nucleotide polymorphisms and somatic mutations

Malignant fibrous histiocytoma—pleomorphic sarcoma, NOS gene expression, histology, and clinical course. A pilot study

Contact Info

Product

Resources

About