Category Archives: publication

From temperature imaging to brain development, including one of our most recurrent topics: cancer. Latest publications of the CMMI.

Photoacoustic temperature imaging based on multi-wavelength excitation.
Meng L, Deschaume O, Larbanoix L, Fron E, Bartic C, Laurent S, Van der Auweraer M, Glorieux C
Photoacoustics 2019 Mar; 13: 33-45

DMRT5, DMRT3, and EMX2 Cooperatively Repress Gsx2 at the Pallium-Subpallium Boundary to Maintain Cortical Identity in Dorsal Telencephalic Progenitors.
Desmaris E, Keruzore M, Saulnier A, Ratié L, Assimacopoulos S, De Clercq S, Nan X, Roychoudhury K, Qin S, Kricha S, Chevalier C, Lingner T, Henningfeld KA, Zarkower D, Mallamaci A, Theil T, Campbell K, Pieler T, Li M, Grove EA, Bellefroid EJ.
J Neurosci. 2018 Oct 17;38(42):9105-9121. doi: 10.1523/JNEUROSCI.0375-18.2018. Epub 2018 Aug 24.

Inhibition of SHIP2 activity inhibits cell migration and could prevent metastasis in breast cancer cells.
Ghosh S, Scozzaro S, Ramos AR, Delcambre S, Chevalier C, Krejci P, Erneux C.
J Cell Sci. 2018 Aug 16;131(16). pii: jcs216408. doi: 10.1242/jcs.216408.

YAP and TAZ are essential for basal and squamous cell carcinoma initiation.
Debaugnies M, Sánchez-Danés A, Rorive S, Raphaël M, Liagre M, Parent MA, Brisebarre A, Salmon I, Blanpain C.
EMBO Rep. 2018 Jul;19(7). pii: e45809. doi: 10.15252/embr.201845809. Epub 2018 Jun 6.

Summer publications of the CMMI/Special focus: how do cells decode the various Wnt signaling pathways

Wnt signaling is key to several important processes, both in health and disease. The genes encoding the Wnt ligand and its receptor Frizzled have undergone extensive duplications during evolution, but how vertebrate cells are able to “decode” their 19 Wnt ligands and therefore make a variety of functions emerge from this genetic diversity was still largely unknown.

In “A molecular mechanism for Wnt ligand-specific signaling”, published this summer in Science, our colleague Benoit Vanhollebeke, his team and collaborators from the UCL NanoBiophysics Lab and Max Planck Institute for lung and heart research found some important pieces of the puzzle of Wnt signaling diversity. They dissect the molecular mechanism for Wnt7-specific signaling and unravel the central role played by Reck, GPR124 and Dishevelled the process. It can be hypothesized that other Wnt or Frizzled family members are decoded in a similar manner through other accessory proteins.

 

A molecular mechanism for Wnt ligand-specific signaling.
Eubelen M, Bostaille N, Cabochette P, Gauquier A, Tebabi P, Dumitru AC, Koehler M, Gut P, Alsteens D, Stainier DYR, Garcia-Pino A, Vanhollebeke B.
Science. 2018 Aug 17;361(6403). pii: eaat1178. Epub 2018 Jul 19.

Summer publications of the CMMI/Special focus: research in image analysis conducted by the DIAPath team of the CMMI

Image analysis is one of the strong points of our digital pathology team DIAPath. In a recent article, our colleagues at DIAPath explain how they used deep learning and data augmentation techniques to automate annotation of histological slide images from colorectal tissue. Their method segments glandular epithelium in images from tissue slides stained with hemaetoxylin & eosin or by immunohistochemistry (IHC). It is robust, outperforms pre-existing methods and concurs highly with manual annotations, thereby enabling the compatimentalization of IHC quantification.

Segmentation of glandular epithelium in colorectal tumours to automatically compartmentalise IHC biomarker quantification: A deep learning approach.
Van Eycke YR, Balsat C, Verset L, Debeir O, Salmon I, Decaestecker C.
Med Image Anal. 2018 Jul 12;49:35-45.

Summer publications of the CMMI

What an exciting year! Many articles that benefited from the team and/or infrastructure of the CMMI were published in the last months. Some of them are below. A special focus on two additional CMMI articles will follow in the coming days. Congratulations to our collaborators for the good work!

Silencing of casein kinase 1 delta reduces migration and metastasis of triple negative breast cancer cells.
Bar I, Merhi A, Larbanoix L, Constant M, Haussy S, Laurent S, Canon JL, Delrée P.
Oncotarget. 2018 Jul 20;9(56):30821-30836. eCollection 2018 Jul 20

Activation of the endoplasmic reticulum stress sensor IRE1α by the vaccine adjuvant AS03 contributes to its immunostimulatory properties.
Givord C, Welsby I, Detienne S, Thomas S, Assabban A, Lima Silva V, Molle C, Gineste R, Vermeersch M, Perez-Morga D, Leo O, Collignon C, Didierlaurent AM, Goriely S.
NPJ Vaccines. 2018 Jun 28; 3:20. eCollection 2018.

Chitosan-coated liposome dry-powder formulations loaded with ghrelin for nose-to-brain delivery.
Salade L, Wauthoz N, Vermeersch M, Amighi K, Goole J.
Eur J Pharm Biopharm. 2018 Aug; 129:257-266. Epub 2018 Jun 15.

Effects of press-fit biphasic (collagen and HA/βTCP) scaffold with cell-based therapy on cartilage and subchondral bone repair knee defect in rabbits.
Hernigou J, Vertongen P, Chahidi E, Kyriakidis T, Dehoux JP, Crutzen M, Boutry S, Larbanoix L, Houben S, Gaspard N, Koulalis D, Rasschaert
J. Int Orthop. 2018 Jun 7.

Early spring publications of the CMMI: congratulations to our collaborators!

Conformation-dependent partitioning of yeast nutrient transporters into starvation-protective membrane domains.
Gournas C, Gkionis S, Carquin M, Twyffels L, Tyteca D, André B.
Proc Natl Acad Sci U S A. 2018 Mar 20. pii: 201719462. doi: 10.1073/pnas.1719462115

The plasma membrane of eukaryotic cells is compartmentalized into domains enriched in specific lipids and proteins. However, our understanding of the mechanisms and functions of this lateral segregation remains incomplete. In this study led by Christos Gournas from the Molecular Physiology of the Cell lab (ULB), we report that the clustering of the yeast Can1 arginine transporter into domains is dictated by its conformation and requires sustained biogenesis of complex sphingolipids. Furthermore, this clustering confers to Can1 and other transporters protection from ubiquit-independent endocytosis. Under nutrient starvation conditions, this protective role is reinforced, thereby allowing cells to preserve a fraction of their nutrient transporters from bulk endocytosis and to more efficiently resume growth when replenishing compounds are available. Our study reveals nutrient-regulated protection from endocytosis as an important role for protein partitioning into membrane domains.02The images above were acquired on the CMMI’s Zeiss LSM710, using its Airy Scan module. Shown are surface section of an art1Δ bul1/2Δ gap1Δ can1Δ PIL1-mCherry yeast strain expressing Can1-GFP, Can1(T180R)-GFP, or Can1(S176N,T456S)-GFP. Can1(T180R) is a loss-of-function mutant of Can1 that is unable to bind Arg. Can1(S176N,T456S) is a mutant converted into a Lys-scpecific transporter. Taken together with additional data in the article, these observations demonstrated that substrate transport abolishes Can1 EMC clustering. Conditions and quantifications (n = 32–42) are as in B. ***P < 0.001; ns, nonsignificant, P > 0.05. (Scale bar: 2 μm.).

New Folate-Grafted Chitosan Derivative To Improve Delivery of Paclitaxel-Loaded Solid Lipid Nanoparticles for Lung Tumor Therapy by Inhalation.
Rosière R, Van Woensel M, Gelbcke M, Mathieu V, Hecq J, Mathivet T, Vermeersch M, Van Antwerpen P, Amighi K, Wauthoz N.
Mol Pharm. 2018 Mar 5;15(3):899-910. doi: 10.1021/acs.molpharmaceut.7b00846. Epub 2018 Jan 30

Inhaled chemotherapy for the treatment of lung tumors requires that drug delivery systems improve selectivity
for cancer cells and tumor penetration and allow sufficient lung residence. The study led by Rémi Rosière from the Laboratoire de Pharmacie Galénique et Biopharmacie demonstrates the positive impact of using coated “solid lipid nanoparticles” on the delivery of paclitaxel by inhalation.03The CMMI’s contribution to the study was to image solid lipid nanoparticles by transmission electron microscopy. The figure above compares the morphology of paclitaxel-loaded solid lipid nanoparticles with or without F-PEG-HTCC coating. Scale bar: 200 nm.

A prospective clinical study of the implications of IL-8 in the diagnosis, aggressiveness and prognosis of prostate cancer.
Roumeguère T, Legrand F, Rassy EE, Kaitouni MI, Albisinni S, Rousseau A, Vanhaeverbeek M, Rorive S, Decaestecker C, Debeir O, Boudjeltia KZ, Aoun F.
Future Sci OA. 2017 Nov 15;4(2):FSO266. doi: 10.4155/fsoa-2017-0084. eCollection 2018 Feb.

In this collaborative clinical study, researchers from three hospitals (Erasme hospital in Brussels, André Vésale Hospital in Charleroi and Hôtel Dieu de France Hospital in Beirut) as well as from the CMMI investigate the relationship between the IL-8 cytokine and prostate cancer. They conclude that IL-8 serum level is not a significant predictor of diagnosis, aggressiveness or prognosis of prostate cancer.

With a little delay, here are some of the winter publications of the CMMI…

Murine stroma adopts a human-like metabolic phenotype in the PDX model of colorectal cancer and liver metastases.
Blomme A, Van Simaeys G, Doumont G, Costanza B, Bellier J, Otaka Y, Sherer F, Lovinfosse P, Boutry S, Palacios AP, De Pauw E, Hirano T, Yokobori T, Hustinx R, Bellahcène A, Delvenne P, Detry O, Goldman S, Nishiyama M, Castronovo V, Turtoi A.
Oncogene. 2018 Mar;37(9):1237-1250. doi: 10.1038/s41388-017-0018-x. Epub 2017 Dec 15.

Cancer research is increasingly dependent of patient-derived xenograft model (PDX). However, a major point of concern regarding the PDX model remains the replacement of the human stroma with murine counterpart. The present study investigates this issue in PDX models of colorectal cancer and liver metastasis, with an approach combining metabolomics (MALDI imaging) and the measurement of glucose uptake by in vivo PET. The data show for the first time that CRC/CRC-LM PDX model maintains the functional stability at the metabolic level despite the early replacement of the human stroma by murine cells. The findings demonstrate that human cancer cells actively educate murine stromal cells during PDX development to adopt the human-like phenotype.

01The inner-rod component of Shigella flexneri type 3 secretion system, MxiI, is involved in the transmission of the secretion activation signal by its interaction with MxiC.
El Hajjami N, Moussa S, Houssa J, Monteyne D, Perez-Morga D, Botteaux A.
Microbiologyopen. 2018 Feb;7(1). doi: 10.1002/mbo3.520. Epub 2017 Dec 1.

Development of coated liposomes loaded with ghrelin for nose-to-brain delivery for the treatment of cachexia.
Salade L, Wauthoz N, Deleu M, Vermeersch M, De Vriese C, Amighi K, Goole J.
Int J Nanomedicine. 2017 Nov 28;12:8531-8543. doi: 10.2147/IJN.S147650. eCollection 2017.

A nanobody-based tracer targeting DPP6 for non-invasive imaging of human pancreatic endocrine cells.
Balhuizen A, Massa S, Mathijs I, Turatsinze JV, De Vos J, Demine S, Xavier C, Villate O, Millard I, Egrise D, Capito C, Scharfmann R, In’t Veld P, Marchetti P, Muyldermans S, Goldman S, Lahoutte T, Bouwens L, Eizirik DL, Devoogdt N.
Sci Rep. 2017 Nov 9;7(1):15130. doi: 10.1038/s41598-017-15417-2.

The CMMI is happy to announce the publication of a study led by our colleagues of the Molecular Physiology of the Cell lab of the ULB.
Congratulations to Céline Barthelemy, Abdoulaye Oury BARRY and Bruno André as well as to our deputy director Laure Twyffels who contributed to the confocal fluorescence microscopy part.

The study explores the effect of the anticancer agent FTY720 on yeast and human cells. FTY720 was already known to “starve cancer cells to death” (10.1002/1873-3468.12121).  The present study better explains how: it shows that FTY720 reduces the activity of several plasma membrane amino acids permeases. This decreases the ability of cells to import amino acids, which, in turn, triggers a positive feed-back mechanism that leads to the endocytosis of these permeases via the inhibition of TORC1, and a further decrease in amino acid import capability.

news01

Humans are protected against African trypanosomes by the serum protein APOL1; however, Trypanosoma rhodesiense and Trypanosoma gambiense neutralize this defense and cause sleeping sickness. Fontaine et al. found that APOL3 is also able to kill both species and consequently engineered a therapeutic version of APOL1 that eradicates infection by T. gambiense in mice.

APOLs with low pH dependence can kill all African trypanosomes
publication_22-09-2017

TEM imaging of T.b. brucei during lysis

Frédéric Fontaine, Laurence Lecordier, Gilles Vanwalleghem, Pierrick Uzureau, Nick Van Reet, Martina Fontaine, Patricia Tebabi, Benoit Vanhollebeke, Philippe Büscher, David Pérez-Morga and Etienne Pays

The CMMI is proud to announce the publication of an article to which it contributed

The CMMI is proud to announce the publication of an article to which it contributed:

CDK4 phosphorylation status and a linked gene expression profile predict sensitivity to palbociclib.

Raspé E, Coulonval K, Pita JM, Paternot S, Rothé F, Twyffels L, Brohée S, Craciun L, Larsimont D, Kruys V, Sandras F, Salmon I, Van Laere S, Piccart M, Ignatiadis M, Sotiriou C, Roger PP.
EMBO Mol Med. 2017 May 31. pii: e201607084. doi: 10.15252/emmm.201607084.
PMID: 28566333
We contributed to the development and execution of an assay that measures the sensitivity of cancer cell lines to a chemotherapeutic agent named palbociclib or PD0332991.

How does it work?
The assay is based on the fluorescent detection of BrdU, a nucleotide analog that can be incorporated into the DNA by cells that are actively replicating their DNA. An additional DAPI staining of all nuclei is performed. As a result, the nuclei of DNA-replicating cells emit green and blue fluorescence, while other nuclei emit blue fluorescence only.
Here, the classical BrdU incorporation assay was adapted into a 96-well format, in order to establish dose-response curves for >20 breast cell lines treated with various doses of palbociclib (PD0332991). The CMMI contributed to image acquisition and analysis, which was performed via a custom-made ImageJ routine. The ouput was a measure of the proportion of cells in S-phase for each experimental condition.

And the results?
We verified that our assay was more sensitive than the classical sulforhodamine and MTT assays, which only reflect cell accumulation and viability, respectively. The results confirmed our collaborators’ hypothesis that the T172 phosphorylation of CDK4 (which is the molecular target of PD0332991) correctly predicts the sensitivity or insensitivity of the cells lines to palbociclib.
Finally, to overcome the difficulty of using post-translational modification analysis of CDK4 in the clinic, our collaborators developed a surrogate CDK4 modification signature based on the expression of 11 genes. The signature correctly predicts the CDK4 modification profile of tumors and breast cancer cell lines, and the sensitivity of the latter to palbociclib. It may therefore be adapted to optimize the use of palbociclib in the clinic and extend its current indication to additional types of breast tumors.

Congratulations to Pierre Roger and his team, and in particular to Eric Raspé!