scholarly journals Dynamics of 3D carcinoma cell invasion into aligned collagen

2018 ◽  
Vol 10 (2) ◽  
pp. 100-112 ◽  
Author(s):  
Arja Ray ◽  
Rachel K. Morford ◽  
Nima Ghaderi ◽  
David J. Odde ◽  
Paolo. P. Provenzano
Keyword(s):  
Extracellular Matrix ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Carcinoma Cell ◽  
Spatiotemporal Dynamics ◽  
Contact Inhibition ◽  
Contact Guidance ◽  
Cell Behavior ◽  
Cancer Cell Invasion ◽  
Invasive Front

We present a novel platform to quantify spatiotemporal dynamics of cell behavior at and beyond the invasive front and demonstrate that contact inhibition and contact guidance orchestrate cancer cell invasion into anisotropic extracellular matrix.

scholarly journals A new biomimetic assay reveals the temporal role of matrix stiffening in cancer cell invasion

2018 ◽  
Vol 29 (25) ◽  
pp. 2979-2988 ◽  
Author(s):  
Ralitza Staneva ◽  
Federica Burla ◽  
Gijsje H. Koenderink ◽  
Stéphanie Descroix ◽  
Danijela Matic Vignjevic ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Early Stage ◽  
In Vitro Models ◽  
Surrounding Tissue ◽  
Cancer Cell Invasion ◽  
Temporal Dimension ◽  
Vitro Assay

Tumor initiation and growth is associated with significant changes in the surrounding tissue. During carcinoma progression, a global stiffening of the extracellular matrix is observed and is interpreted as a signature of aggressive invasive tumors. However, it is still unknown whether this increase in matrix rigidity promotes invasion and whether this effect is constant along the course of invasion. Here we have developed a biomimetic in vitro assay that enabled us to address the question of the importance of tissue rigidity in the chronology of tumor invasion. Using low concentrations of the sugar threose, we can effectively stiffen reconstituted collagen I matrices and control the stiffening in time with no direct effect on residing cells. Our findings demonstrate that, depending on the timing of its stiffening, the extracellular matrix could either inhibit or promote cancer cell invasion and subsequent metastasis: while matrix stiffening after the onset of invasion promotes cancer cell migration and tumor spreading, stiff matrices encapsulate the tumor at an early stage and prevent cancer cell invasion. Our study suggests that adding a temporal dimension in in vitro models to analyze biological processes in four dimensions is necessary to fully capture their complexity.

scholarly journals Protein kinase D2 induces invasion of pancreatic cancer cells by regulating matrix metalloproteinases

2014 ◽  
Vol 25 (3) ◽  
pp. 324-336 ◽  
Author(s):  
Christoph Wille ◽  
Conny Köhler ◽  
Milena Armacki ◽  
Arsia Jamali ◽  
Ulrike Gössele ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Extracellular Matrix ◽  
Protein Kinase ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Pancreatic Cancer Cell ◽  
Therapeutic Strategies ◽  
Cancer Cell Invasion ◽  
Pancreatic Cancer Cells

Pancreatic cancer cell invasion, metastasis, and angiogenesis are major challenges for the development of novel therapeutic strategies. Protein kinase D (PKD) isoforms are involved in controlling tumor cell motility, angiogenesis, and metastasis. In particular PKD2 expression is up-regulated in pancreatic cancer, whereas PKD1 expression is lowered. We report that both kinases control pancreatic cancer cell invasive properties in an isoform-specific manner. PKD2 enhances invasion in three-dimensional extracellular matrix (3D-ECM) cultures by stimulating expression and secretion of matrix metalloproteinases 7 and 9 (MMP7/9), by which MMP7 is likely to act upstream of MMP9. Knockdown of MMP7/9 blocks PKD2-mediated invasion in 3D-ECM assays and in vivo using tumors growing on chorioallantois membranes. Furthermore, MMP9 enhances PKD2-mediated tumor angiogenesis by releasing extracellular matrix–bound vascular endothelial growth factor A, increasing its bioavailability and angiogenesis. Of interest, specific knockdown of PKD1 in PKD2-expressing pancreatic cancer cells further enhanced the invasive properties in 3D-ECM systems by generating a high-motility phenotype. Loss of PKD1 thus may be beneficial for tumor cells to enhance their matrix-invading abilities. In conclusion, we define for the first time PKD1 and 2 isoform–selective effects on pancreatic cancer cell invasion and angiogenesis, in vitro and in vivo, addressing PKD isoform specificity as a major factor for future therapeutic strategies.

scholarly journals Collective cancer cell invasion requires RNA accumulation at the invasive front

2020 ◽  
Vol 117 (44) ◽  
pp. 27423-27434 ◽  
Author(s):  
George Chrisafis ◽  
Tianhong Wang ◽  
Konstadinos Moissoglu ◽  
Alexander N. Gasparski ◽  
Yeap Ng ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Cancer Progression ◽  
Cell Invasion ◽  
Single Cells ◽  
Three Dimensional ◽  
Nucleotide Exchange ◽  
Cancer Cell Invasion ◽  
Invasive Front ◽  
Rna Accumulation

Localization of RNAs at protrusive regions of cells is important for single-cell migration on two-dimensional surfaces. Protrusion-enriched RNAs encode factors linked to cancer progression, such as the RAB13 GTPase and the NET1 guanine nucleotide exchange factor, and are regulated by the tumor-suppressor protein APC. However, tumor cells in vivo often do not move as single cells but rather utilize collective modes of invasion and dissemination. Here, we developed an inducible system of three-dimensional (3D) collective invasion to study the behavior and importance of protrusion-enriched RNAs. We find that, strikingly, both theRAB13andNET1RNAs are enriched specifically at the invasive front of leader cells in invasive cell strands. This localization requires microtubules and coincides with sites of high laminin concentration. Indeed, laminin association and integrin engagement are required for RNA accumulation at the invasive front. Importantly, perturbing RNA accumulation reduces collective 3D invasion. Examination of in vivo tumors reveals a similar localization of theRAB13andNET1RNAs at potential invasive sites, suggesting that this mechanism could provide a targeting opportunity for interfering with collective cancer cell invasion.

scholarly journals Linearized texture of three-dimensional extracellular matrix is mandatory for bladder cancer cell invasion

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Massimo Alfano ◽  
Manuela Nebuloni ◽  
Raffaele Allevi ◽  
Pietro Zerbi ◽  
Erika Longhi ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Bladder Cancer ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Three Dimensional ◽  
Bladder Cancer Cell ◽  
Cancer Cell Invasion
Sign in / Sign up

Export Citation Format

Share Document