Extracellular matrix determinants and the regulation of cancer cell invasion stratagems

Willis, Amanda L.; Sabeh, Farideh; Li, X.-Y.; Weiss, Stephen J.

doi:10.1111/jmi.12064

Cited by 76 publications

(68 citation statements)

References 131 publications

(241 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…MMP14 is the major pericellular collagenase, which also cleaves cell-surface proteins, thus enhancing junctional disassembly and mesenchymal invasion of tumor cells across tissue barriers (8,29,32). Our results reveal a novel concept, whereby MMP16, rather than inducing cell dissociation and mesenchymal invasion, regulates tumor progression by impeding pericellular collagen degradation and supporting tumor cell-cell adhesion via posttranslational MMP14 downregulation.…”

Section: Discussionmentioning

confidence: 79%

See 1 more Smart Citation

MMP16 Mediates a Proteolytic Switch to Promote Cell–Cell Adhesion, Collagen Alignment, and Lymphatic Invasion in Melanoma

et al. 2015

View full text Add to dashboard Cite

Lymphatic invasion and accumulation of continuous collagen bundles around tumor cells are associated with poor melanoma prognosis, but the underlying mechanisms and molecular determinants have remained unclear. We show here that a copy-number gain or overexpression of the membranetype matrix metalloproteinase MMP16 (MT3-MMP) is associated with poor clinical outcome, collagen bundle assembly around tumor cell nests, and lymphatic invasion. In cultured WM852 melanoma cells derived from human melanoma metastasis, silencing of MMP16 resulted in cell-surface accumulation of the MMP16 substrate MMP14 (MT1-MMP) as well as L1CAM cell adhesion molecule, identified here as a novel MMP16 substrate. When limiting the activities of these trans-membrane protein substrates toward pericellular collagen degradation, cell junction disassembly, and blood endothelial transmigration, MMP16 supported nodular-type growth of adhesive collagen-surrounded melanoma cell nests, coincidentally steering cell collectives into lymphatic vessels. These results uncover a novel mechanism in melanoma pathogenesis, whereby restricted collagen infiltration and limited mesenchymal invasion are unexpectedly associated with the properties of the most aggressive tumors, revealing MMP16 as a putative indicator of adverse melanoma prognosis. Cancer Res; 75(10); 2083-94. Ó2015 AACR.

show abstract

Section: Discussionmentioning

confidence: 79%

“…Membrane-type matrix metalloproteinases (MT-MMP) are pericellular ECM-degrading proteases with substrate specificities ranging from fibrillar collagens and fibrin to basement membrane (BM) components (8,9). They also cleave cell-surface-associated molecules and activate secreted MMPs (10).…”

Section: Introductionmentioning

confidence: 99%

MMP16 Mediates a Proteolytic Switch to Promote Cell–Cell Adhesion, Collagen Alignment, and Lymphatic Invasion in Melanoma

et al. 2015

View full text Add to dashboard Cite

show abstract

“…In the context of tumor growth, penetration of the BM is important as the BM functions as a barrier and differentiates between non-invasive and invasive tumor growth. MMPs are known to degrade ECM substrates and promote the invasion of tumorous vasculature (46). The role of MMP-9 is decisive as it dissolves the BM by degrading type IV and V collagen (22).…”

Section: Discussionmentioning

confidence: 99%

Effect of selective small molecule inhibitors on MMP-9 and VEGFR-1 expression in p16-positive and -negative squamous cell carcinoma

Kramer

Schultz²,

Hock

et al. 2017

Oncology Letters

View full text Add to dashboard Cite

Abstract. The identification of molecular targets in the therapy of human papilloma virus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is a primary aim of cancer research. Matrix metalloproteinase 9 (MMP-9) and vascular endothelial growth factor receptor (VEGFR) have important roles in the development of HNSCC. The tyrosine kinase inhibitors, nilotinib, dasatinib, erlotinib and gefitinib are well established in the targeted therapy of tumors other than HNSCC. The present study aimed to investigate the alteration of MMP-9 and VEGFR-1 expression patterns following treatment with these tyrosine kinase inhibitors in p16-positive and -negative squamous carcinoma cells. MMP-9 and VEGFR-1 expression was evaluated using an ELISA in HNSCC 11A, HNSCC 14C and p16-positive CERV196 tumor cell lines, following treatment with nilotinib, dasatinib, erlotinib and gefitinib. A statistically significant reduction in MMP-9 and VEGFR-1 expression was observed in the p16-negative HNSCC 11A cells following treatment with all inhibitors (P<0.05). VEGFR-1 expression was significantly increased in p16-positive SCC cells following treatment with nilotinib, dasatinib, erlotinib and gefitinib (P<0.05). The expression of MMP-9 and VEGFR-1 was significantly altered by treatment with nilotinib, dasatinib, erlotinib and gefitinib in vitro. The results of the present study are attributed to the efficacy of the tested drugs and present potential compensatory strategies of cancer cells to avoid the antiangiogenic properties of the tested tyrosine kinase inhibitors in vitro.

show abstract

“…Proteolytic enzymes, which are secreted into ECM, have important roles in tumor formation and progression. 28 A great deal of MMPs and ADAMTS have played role in these processes. MMPs degrade collagen and elastin in ECM and degradation of collagen is one of the most important events in invasion and metastasis.…”

Section: Discussionmentioning

confidence: 99%

Changes of the Expressions of Orphan and gon- ADAMTS in Chondrosarcoma Cells

Işık¹

2015

UHOD

View full text Add to dashboard Cite

Some of A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) enzymes have been suggested to facilitate invasion and metastasis in cancer. ADAMTS20 is called gon-ADAMTS and ADAMTS10 and -17 are called orphan ADAMTSs. ADAMTS20 degrades versican and aggrecan in extracellular matrix. We aimed to investigate the effects of insulin on ADAMTS10,-17 and -20 in OUMS-27 chondrosarcoma cells. OUMS-27 cells were cultured in Dulbecco's modified Eagle' medium (DMEM) containing 10 μg/mL insulin. The medium was changed every other day up to 11th day. Cells were harvested at 1, 3, 7, and 11th days and RNA isolation was performed at appropriate times according to study setup. The levels of RNA expression of ADAMTS10,-17 and -20 were estimated by qRT-PCR using appropriate primers. ADAMTS10 mRNA expression gradually decreased within 7 days after insulin induction compared to control group. There was a significant difference between control and Day 7 groups (p=0.021) as well as Day 1 and Day 7 groups (p=0.028). ADAMTS17 mRNA expression increased right after insulin induction at day 1 compared to control group and protected its high levels throughout insulin application. The most evident and statistically significant increase in mRNA concentration was observed at day 7 after insulin induction (p= 0.014). Our results demonstrated that ADAMTS10,-17 and -20 might have a role in cancer progression. Although functions of ADAMTS10 and -17 are not known, their expression levels have changed in chondrosarcoma cell line. Further studies are needed to characterize chondrosarcoma cells because of the possible association between cancer progression and ADAMTS proteins. Keywords: ADAMTS, Chondrosarcoma, Insulin, qRT-PCR, OUMS-27 ÖZET Kondrosarkom Hücrelerinde Orfan ve gon-ADAMTS'ların Ekspresyonundaki DeğişimlerA disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) enzimlerinden bazılarının kanserde invazyon ve metastazı kolaylaştıracağı öngörülmektedir. ADAMTS20, gon-ADAMTS olarak ve ADAMTS10 ile -17, orfan ADAMTS olarak adlandırılır. Bunlardan ADAMTS20 hücre dışı matrikste versikan ve agrekanı parçalayan enzim olarak bilinir. Bu çalışmada OUMS-27 hücrelerinde insülinin ADAMTS10, -17 ve -20 üzerine etkilerinin araştırılması amaçlandı. OUMS-27 hücreleri 10 μg/ml insülin içeren Dulbecco's Modified Eagle Medium (DMEM) ortamında kültüre edildiler. Medyum 11. güne kadar iki günde bir değiştirildi. Hücreler 1, 3, 7 ve 11. günlerde toplandı ve her birinde aynı gün RNA izolasyonları gerçekleştirildi. ADAMTS10, -17 ve -20'nin RNA ekspresyon düzeyleri uygun primerler kullanılarak qRT-PCR ile hesaplandı. Kontrol grubuyla karşılaştırıldığında, ADAMTS10 mRNA ekspresyonu insülin indüksiyonundan sonra 7 gün içinde gittikçe azalmıştır. Kontrol ile 7. gün grubu arasında (p=0.021) ve 1. gün ve 7. gün grubu (p=0.028) arasında anlamlı farklılıklar vardı. Kontrol grubuyla karşılaştırıldığında ADAMTS17 mRNA ekspresyonu insülin indüksiyonundan hemen sonra 1. günde yükselmiş ve yüksek seviyelerini insülin uygulaması boyunca k...

show abstract

Extracellular matrix determinants and the regulation of cancer cell invasion stratagems

Cited by 76 publications

References 131 publications

MMP16 Mediates a Proteolytic Switch to Promote Cell–Cell Adhesion, Collagen Alignment, and Lymphatic Invasion in Melanoma

MMP16 Mediates a Proteolytic Switch to Promote Cell–Cell Adhesion, Collagen Alignment, and Lymphatic Invasion in Melanoma

Effect of selective small molecule inhibitors on MMP-9 and VEGFR-1 expression in p16-positive and -negative squamous cell carcinoma

Changes of the Expressions of Orphan and gon- ADAMTS in Chondrosarcoma Cells

Contact Info

Product

Resources

About