IP3D

Innovation for the study of tumor cell Proliferation in 3D

Therapeutic options for cancer have considerably improved over the last decades thanks to a better understanding of cancer cell biology and to the development of 3D tumor models that integrate essential parameters such as cellular heterogeneity, cell-cell and cell-microenvironment interactions.

The aim of our work is to study the mechanisms that control and regulate proliferation dynamics in relation with the organization in 3D of a tumor cell population. We focus on: (i) the regulation of the aggregation of tumor cells to form 3D clusters, (ii) the regulation of the dynamics of proliferation of tumor microdomains in 3D. We investigate how these processes are controlled by the microenvironment, the cell cycle regulation, and the intercellular dialogue. Our work relies on genetically engineered cells expressing fluorescent reporters and biomarkers that are accessible to innovative microscopy strategies both on live or fixed samples and on the development of in vitro assays.

 

These innovations are implemented to explore the dynamics of the response to anticancer drugs and to develop innovative models for the pharmacological evaluation of new therapeutic agents.

Team leader

Valérie lobjois
Valérie Lobjois

Main points

Selected publications
  • Gomes, A., Defaux, M., Michel Lemee, R., Lobjois, V. and Ducommun, B. – Reversible growth arrest of spheroids stored in oxygen absorber-induced anoxia. Oncology Lett. (2018) doi: 10.3892/ol.2017.7465.
  • Gava, F., Ducommun, B. and Lobjois, V. Anchorage-independent tumor cells clustering and implication in metastatic dissemination. Cancer Therapy & Oncology Int J. 6(2) (2017)
  • Leroy-Lerêtre, M., Dimarco, G., Cazales, M., Boizeau, ML., Ducommun, B., Lobjois, V. and Degond, P. – Are tumor cell lineages solely shaped by mechanical forces? Bull. Math. Biol. (2017) DOI 10.1007/s11538-017-0333-y
  • Pinkerton, N., Frongia, C., Lobjois, V., Wilson, BK., Bruzek, MJ., Prud’Homme, RK., Anthony, J., Bolzed, F. and Chassaing, S. – Red-emitting, EtTP-5-based organic nanoprobes for two-photon imaging in 3D multicellular biological models. RSC Adv., 2016, 6, 65770–65774
  • Gomes, A., Russo, A., Vidal, G., Demange, E., Pannetier, P., Souguir, Z., Lagarde, J-M., Ducommun, B. and Lobjois, V. – Evaluation by quantitative image analysis of anticancer drug activity on multicellular spheroids grown in 3D matrix. Oncol Lett 12: 4371-4376, 2016 DOI: 10.3892/ol.2016.5221
  • Gomes, A., Guillaume, L., Grimes DR., Fehrenbach, J., Ducommun, B. and Lobjois, V. -Oxygen partial pressure is a rate-limiting parameter for cell proliferation in 3D spheroids grown in physioxic culture condition. Plos One (2016) – 11 (8): e0161239. doi:10.1371/journal.pone.0161239
  • Jullien, D., Vignard, J., Fedor, Y., Olichon, A., Favier, J., Crozatier, M. Salles, B., Ducommun, B., Mirey, G. – Nanobody-based universal histone binding domains that associate with chromatin in living cells. J Cell Sci. 2016 Jul 1;129(13):2673-83. doi: 10.1242/jcs.183103.
  • Judée F., Frongia, C., Ducommun, B., Yousfi, M., Lobjois, V. and Merbahi, N. – Short and long time effects of low temperature Plasma Activated Media on 3D multicellular tumor spheroids. Sci Rep. (2016) Feb 22;6:21421. doi: 10.1038/srep21421
  • Masson A., Escande, P., Frongia, C., Clouvel, G., Ducommun, B and Lorenzo, C. – High-resolution in-depth imaging of optically cleared thick samples using an adaptive SPIM. Scientific Reports (2015) doi:10.1038/srep16898
  • Saias, L., Gomes, A., Cazales, M., Ducommun, B. and Lobjois, V. – Cell–cell adhesion and cytoskeleton tension are key but opposing regulators of tumor cell aggregation. Cancer Research (2015) 75(12); 1–8
  • Aoun, L., Weiss, P., Laborde, A., Ducommun, B., Lobjois, V.* and Vieu, C*. – Microdevice arrays of high aspect ratio Poly(DiMethylSiloxane) pillars for the investigation of multicellular tumour spheroid mechanical properties. Lab on a chip (2014) 7;14(13):2344-53* Co-corresponding authors
  • Mondesert, O., Frongia, C., Clayton, O., Boizeau, ML., Ducommun, B. and Lobjois, V. – Monitoring the activation of the DNA damage response pathway in a 3D spheroid model. Plos One 2015 Jul 30;10(7):e0134411. doi: 10.1371/journal.pone.0134411
  • Jeandupeux, E., Lobjois, V. and Ducommun, B. – 3D print customized sample holders for live light sheet microscopy. BBRC (2015) 463: 1141-1143 – 10.1016/j.bbrc.2015.06.072
  • Le Corre G., Weiss P., Ducommun B. and Lorenzo C. – Optical Signature of Multi Cellular Tumor Spheroid using index- mismatch- induced spherical aberrations. Journal of Biomedical Optics SPIE (2014) 8941-36
  • Zhang, W., Fehrenbach, J ., Desmaison, A., Lobjois, A., Ducommun, B. and Weiss, P. – Structure tensor based analysis of cells and nuclei organization in tissues. IEEE Trans Med Imaging. Jan;35(1):294-306. doi: 10.1109/TMI.2015.2470093.
  • Plewa, J-M. Yousfi, M., Frongia, C., Eichwald, O., Ducommun, B., Merbahi, N. and Lobjois, V. – Low temperature plasma-induced antiproliferative effects on multi-cellular tumor spheroids. New Journal of Physics (2014) 16 043027 doi:10.1088/1367-2630/16/4/043027
  • Desmaison, A., Grenier, K., Ducommun, B and Lobjois, V. – Mechanical stress impairs mitosis progression in multi-cellular tumor spheroid. PLOS One (2013 – PLOS One (2013) 8(12):e80447
  • Laurent, J., Frongia, C., Cazales, M., Mondésert, O., Ducommun, B. and Lobjois, V. – Multicellular tumor spheroid models to explore cell cycle checkpoints in 3D. MBC Cancer (2013) 8;13:73
  • Jorand, R., Le Corre, G., Andilla, J., Maandhui, A., Frongia, C., Lobjois, V., Ducommun, B. and Lorenzo, C. – Deep and clear optical imaging of thick inhomogeneous samples. PLOS One (2012) 7(4):e35795
Team members
  • Valérie LOBJOIS (MCU),
  • Bernard DUCOMMUN (PUPH, co-team leader),
  • Odile MONDESERT (engineer),
  • Aurélie GOMES (CIFRE thesis),
  • Ludivine GUILLAUME (engineer),
  • Fabien GAVA (PhD student),
  • Lise RIGAL (IE CDD),
  • Julia Bonnet (PhD student)
Collaborations
  • Collaboration with IMACTIV-3D (Centre Pierre Potier)
  • Collaboration VORTEX team (Institut de Recherche en Informa-tique de Toulouse) and ONKO3D team (ITAV)
  • Katia GRENIER (LAAS, Toulouse) – Project funded by ANR-DGA
  • Gladys Mirey (INRA, Toulouse) – Project funded by ANR
  • Toulouse Tech Transfer (SATT Toulouse-Midi-Pyrénées)
Patents

PROCEDE D’IMPLANTATION D’AMAS CELLULAIRE DANS UN EXPLANT DE PEAU

Jardet Claire, Lobjois Valérie, Kurdykowshi Sandrine, Ducommun Bernard et Descargues Pascal
10/02/2015 sous le N° FR 15/00262.
Publié le 18-08-2016 sous le n° WO2016128135

SPHEROIDES MIXTES DE MELANOCYTES ET DE KERATINOCYTES

M. Norlund, V. Lobjois, P. Bedos, B. Ducommun
30/10/2014 sous le N° FR 1460467.
Publié le 6 mai 2016 sous le n°WO2016067240

DISPOSITIF POUR LA COMPRESSION D’UN ECHANTILLON BIOLOGIQUE, SYSTEME ET BANC DE MESURE DE LA RIGIDITE D’UN ECHANTILLON COMPRENANT UN TEL DISPOSITIF

L. Guillaume, O. Guenat, B. Ducommun, V. Lobjois
21/09/2017 sous le numéro FR1758730
Publié le 6 mai 2016 sous le n°WO2016067240

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