This research was presented by Dr. Emil Lou as part of the Special Interest Subgroup V presentation entitled “Tunneling Nanotubes, Cytonemes, and More: Highways for Cell-to-Cell Communication from Development to Disease,” Saturday, December 6, 2014, at the 2014 ASCB/IFCB Annual Meeting in Philadelphia, Pennsylvania. The session was nicely summarized in a write-up by the team at Journal of Cell Biology: http://jcb-biowrites.rupress.org/2014/12/ascb-2014-making-the-connection-between-cytonemes-and-tunneling-nanotubes.html

1. Tunneling nanotubes: role in cancer progression?
Emil Lou, M.D., Ph.D
University of Minnesota
ASCB/IFCB Annual Meeting
Special Interest Session V – Tunneling Nanotubes, Cytonemes, and More
December 6, 2014

2. •This research was presented as part of the Special Interest Subgroup V presentation entitled “Tunneling Nanotubes, Cytonemes, and More: Highways for Cell-to-Cell Communication from Development to Disease,” Saturday, December 6, 2014, at the 2014 ASCB/IFCB Annual Meeting in Philadelphia, Pennsylvania.

3. Following the conversation on #SocialMedia
•Twitter: @cancerassassin1
–I auto-tweeted this presentation, and use Twitter to share information on cancer research and clinical practice of oncology.
–I used the conference hashtag #ASCB2014 for this session, which was Special Interest Subgroup V on Tunneling Nanotubes, Cytonemes, and More, at the ASCB 2014 Annual Meeting (12/6/2014).
–The session was nicely summarized in a write-up by the team at Journal of Cell Biology:
•http://jcb-biowrites.rupress.org/2014/12/ascb-2014-making-the-connection- between-cytonemes-and-tunneling-nanotubes.html
•Links to all papers, Audioslide presentations, etc. are available on the Lou Lab website (umn.edu, search “Lou Lab”)

4. “Social Networking” in Cancer
•Words to describe or characterize communicative activity between cancer cells:
–Coordination – cell signaling; angiogenesis
–Social activity – intercellular/intracellular communication; tumor-stromal interactions
–Social networking – Gap junctions, Exosomes/Microvesicles, Tunneling Nanotubes
–Synchronization – Cell cycle progression; cellular invasion
–Coordinated expression – Altruistic Cell Death leading to resistance

5. Studying tumor cell advancement at the invasive front – modeling tumor invasion and recurrence through examination of TNTs
Scratch assay of MSTO-211H (biphasic mesothelioma cells) – 22-hr time- lapse
Lou et al., PLoS One, 2012 (online suppl video)

6. Cellular Dynamics, Networking, and Tumor Heterogeneity
MSTO-211H cells connected in a syncytial network by TNTs Lou et al., PLoS One, 2012

7. Tumor microenvironment and the role of intercellular communication
•Tumor heterogeneity
–Molecular heterogeneity (e.g. microRNAs)
–Cellular heterogeneity
–Intratumoral vs inter-tumoral heterogeneity
•Tumor-stroma proportions vary between tumor types, and even in the same type of cancer
–Higher proportions have been associated with worse prognosis in several forms of solid tumor malignancies.
•Long-distance communication
–e.g. disruption of gap junctions upon EMT.
–Malignant cells separated by dense tumor matrix in cases of tumors with high stromal density.

8. Lou et al., Pancreas, November 2013

9. Lou et al., PLoS One, 2012

10. Lou et al., PLoS One, 2012 - Figure 1

11. TnT formation is stimulated under conditions of physiologic stress

12. Figure 4, Lou et al., PLoS One, 2012

13. Brightfield time-lapse microscopy of formation of tunneling nanotubes in mesothelioma cell culture
Lou et al., PLoS One, 2012 (video can be found in Supplementary Information online)
MSTO-211H (biphasic mesothelioma cells) – brightfield time-lapse imaging every 15 minutes over 24 hours; video segment over 5-6 hours

14. From 2-D to 3-D study of nanotubes in human tumors
Ady et al., Frontiers in Physiology, Oct 2014

15. Nanotubes in tumors from human mesothelioma and lung adenocarcinoma
Lou et al., PLoS ONE, 2012

17. Thayanithy et al, Experimental Cell Research, 2014

18. Figure 5, Thayanithy et al.,
Exp Cell Res 2014
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2
3
4

19. Thayanithy et al.,
Exp Cell Res 2014

20. Nanotubes in other tumors:
Thayanithy, Dickson, Steer, Subramanian, and Lou. Published in Translational Research, 2014
A), B) orthotopic syngeneic mouse model of osteosarcoma
C) Human epithelial ovarian carcinoma

21. A “Nanotube Index”: Mesothelioma cells form TNTs at a higher rate compared with normal mesothelium
Ady et al., Frontiers in Physiology, Oct 2014

22. TNT length may decrease over time
Ady et al., Frontiers in Physiology, Oct 2014

23. Intercellular transfer of oncomiR-19a between osteosarcoma cells (A), and from osteosarcoma to osteoblasts (B)
Thayanithy et al., Translational Research, 2014

24. SKOV 3 transfected with Alexa488-tagged miRNA 199a (green) transport to IOSE (normal) treated with DiD (red) via a TnT
Thayanithy et al., Translational Research, 2014

25. Lou et al., Pancreas, November 2013

26. Ady et al., Frontiers in Physiology, 2014

27. Ady et al., Frontiers in Physiology, 2014

28. Ady et al., Frontiers in Physiology, 2014 (online video)

29. Research Team:
The Lou Lab – Department of Medicine/Masonic Cancer Center,
University of Minnesota:
Venugopal Thayanithy, PhD – Research Associate/Postdoctoral Fellow
Phillip Wong, MS – Research Technician
Snider Desir – IBP Graduate Student
Collaborators:
University of Minnesota:
Clifford Steer, MD – Department of Medicine
Subbaya Subramanian, PhD – Department of Surgery
MSKCC: Malcolm Moore, D.Phil; Katia Manova-Todorova, PhD; Sho Fujisawa, PhD
City of Hope Cancer Center: Yuman Fong, MD
Obstetrics & Gynecology, Division of Gynecologic Oncology:
Elizabeth Dickson, MD – Gynecologic Oncology Fellow/Lou Lab Fellow
Deanna Teoh, MD – Gynecologic Oncologist
Melissa Geller, MD – Gynecologic Oncologist
Peter Argenta, MD – Collaborator
Biostatistics: Rachel Vogel Isaksson, M.S. and Chap Le, PhD

30. Funding Acknowledgements
•UMN-CTSI KL2 Scholar Award
•National Pancreas Foundation
•American Cancer Society – IRG
•Women’s Health Interdisciplinary Seed Grant, UMN Powell Center
•AACR-GlaxoSmithKline Clinical Scholars Award
•Minnesota Medical Foundation
•Karen Wyckoff Rein in Sarcoma Foundation
•Department of Medicine, Division of HOT
•Baker Street Foundation