Publications by authors named "Janine Terra Erler"

5 Publications

  • Page 1 of 1

Fiber finding algorithm using stepwise tracing to identify biopolymer fibers in noisy 3D images.

Biophys J 2021 09 17;120(18):3860-3868. Epub 2021 Aug 17.

Niels Bohr Institute, University of Copenhagen (UCPH), Copenhagen, Denmark. Electronic address:

We present a novel fiber finding algorithm (FFA) that will permit researchers to detect and return traces of individual biopolymers. Determining the biophysical properties and structural cues of biopolymers can permit researchers to assess the progression and severity of disease. Confocal microscopy images are a useful method for observing biopolymer structures in three dimensions, but their utility for identifying individual biopolymers is impaired by noise inherent in the acquisition process, including convolution from the point spread function (PSF). The new, iterative FFA we present here 1) measures a microscope's PSF and uses it as a metric for identifying fibers against the background; 2) traces each fiber within a cone angle; and 3) blots out the identified trace before identifying another fiber. Blotting out the identified traces in each iteration allows the FFA to detect and return traces of single fibers accurately and efficiently-even within fiber bundles. We used the FFA to trace unlabeled collagen type I fibers-a biopolymer used to mimic the extracellular matrix in in vitro cancer assays-imaged by confocal reflectance microscopy in three dimensions, enabling quantification of fiber contour length, persistence length, and three-dimensional (3D) mesh size. Based on 3D confocal reflectance microscopy images and the PSF, we traced and measured the fibers to confirm that colder gelation temperatures increased fiber contour length, persistence length, and 3D mesh size-thereby demonstrating the FFA's use in quantifying biopolymers' structural and physical cues from noisy microscope images.
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http://dx.doi.org/10.1016/j.bpj.2021.08.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511358PMC
September 2021

Deciphering the temporal heterogeneity of cancer-associated fibroblast subpopulations in breast cancer.

J Exp Clin Cancer Res 2021 May 20;40(1):175. Epub 2021 May 20.

Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Ole Maaløes Vej 5, 2200, Copenhagen N, Denmark.

Background: Cancer-associated fibroblasts (CAFs) comprise a heterogeneous population of stromal cells within the tumour microenvironment. CAFs exhibit both tumour-promoting and tumour-suppressing functions, making them exciting targets for improving cancer treatments. Careful isolation, identification, and characterisation of CAF heterogeneity is thus necessary for ex vivo validation and future implementation of CAF-targeted strategies in cancer.

Methods: Murine 4T1 (metastatic) and 4T07 (poorly/non-metastatic) orthotopic triple negative breast cancer tumours were collected after 7, 14, or 21 days. The tumours were analysed via flow cytometry for the simultaneous expression of six CAF markers: alpha smooth muscle actin (αSMA), fibroblast activation protein alpha (FAPα), platelet derived growth factor receptor alpha and beta (PDGFRα and PDGFRβ), CD26/DPP4 and podoplanin (PDPN). All non-CAFs were excluded from the analysis using a lineage marker cocktail (CD24, CD31, CD45, CD49f, EpCAM, LYVE-1, and TER-119). In total 128 murine tumours and 12 healthy mammary fat pads were analysed.

Results: We have developed a multicolour flow cytometry strategy based on exclusion of non-CAFs and successfully employed this to explore the temporal heterogeneity of freshly isolated CAFs in the 4T1 and 4T07 mouse models of triple-negative breast cancer. Analysing 128 murine tumours, we identified 5-6 main CAF populations and numerous minor ones based on the analysis of αSMA, FAPα, PDGFRα, PDGFRβ, CD26, and PDPN. All markers showed temporal changes with a distinct switch from primarily PDGFRα+ fibroblasts in healthy mammary tissue to predominantly PDGFRβ+ CAFs in tumours. CD26+ CAFs emerged as a large novel subpopulation, only matched by FAPα+ CAFs in abundance.

Conclusion: We demonstrate that multiple subpopulations of CAFs co-exist in murine triple negative breast cancer, and that the abundance and dynamics for each marker differ depending on tumour type and time. Our results form the foundation needed to isolate and characterise specific CAF populations, and ultimately provide an opportunity to therapeutically target specific CAF subpopulations.
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http://dx.doi.org/10.1186/s13046-021-01944-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138934PMC
May 2021

Interplay Between LOX Enzymes and Integrins in the Tumor Microenvironment.

Cancers (Basel) 2019 May 26;11(5). Epub 2019 May 26.

Biotech Research and Innovation Centre (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark.

Members of the lysyl oxidase (LOX) family are secreted copper-dependent amine oxidases that catalyze the covalent crosslinking of collagens and elastin in the extracellular matrix (ECM), an essential process for the structural integrity of all tissues. LOX enzymes can also remodel the tumor microenvironment and have been implicated in all stages of tumor initiation and progression of many cancer types. Changes in the ECM can influence several cancer cell phenotypes. Integrin adhesion complexes (IACs) physically connect cells with their microenvironment. This review article summarizes the main findings on the role of LOX proteins in modulating the tumor microenvironment, with a particular focus on how ECM changes are integrated by IACs to modulate cells behavior. Finally, we discuss how the development of selective LOX inhibitors may lead to novel and effective therapies in cancer treatment.
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http://dx.doi.org/10.3390/cancers11050729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562985PMC
May 2019

Friction-limited cell motility in confluent monolayer tissue.

Phys Biol 2018 07 25;15(6):066004. Epub 2018 Jul 25.

Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark.

Mechanical forces are important factors in the development, coordination and collective motion of cells. Based on a continuum-scale model, we consider the influence of substrate friction on cell motility in confluent living tissue. We test our model on the experimental data of endothelial and cancer cells. In contrast to the commonly used drag friction, we find that solid friction best captures the cell speed distribution. From our model, we quantify a number of measurable physical tissue parameters, such as the ratio between the viscosity and substrate friction.
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http://dx.doi.org/10.1088/1478-3975/aacedcDOI Listing
July 2018

Dynamics of cancerous tissue correlates with invasiveness.

Sci Rep 2017 03 6;7:43800. Epub 2017 Mar 6.

Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, 2100 Copenhagen, Denmark.

Two of the classical hallmarks of cancer are uncontrolled cell division and tissue invasion, which turn the disease into a systemic, life-threatening condition. Although both processes are studied, a clear correlation between cell division and motility of cancer cells has not been described previously. Here, we experimentally characterize the dynamics of invasive and non-invasive breast cancer tissues using human and murine model systems. The intrinsic tissue velocities, as well as the divergence and vorticity around a dividing cell correlate strongly with the invasive potential of the tissue, thus showing a distinct correlation between tissue dynamics and aggressiveness. We formulate a model which treats the tissue as a visco-elastic continuum. This model provides a valid reproduction of the cancerous tissue dynamics, thus, biological signaling is not needed to explain the observed tissue dynamics. The model returns the characteristic force exerted by an invading cell and reveals a strong correlation between force and invasiveness of breast cancer cells, thus pinpointing the importance of mechanics for cancer invasion.
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http://dx.doi.org/10.1038/srep43800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338316PMC
March 2017
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