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J Cancer Metastasis Treat 2020;6:5 I http://dx.doi.org/10.20517/2394-4722.2020.13 Page 23 of 38

Autophagy, a lysosome-driven catabolic process for degradation of self-constituents, participates in the
stress response for maintaining cell homeostasis. It has been shown that autophagy is down-regulated
during cell locomotion, while it is induced when cells arrest their migration.

We found that pro-inflammatory cytokines promote cancer cell migration following down-regulation of
autophagy in the migratory cells. We also investigated at the molecular level the mechanisms through
which the cytokines modulate autophagy.

Our data highlight the role of autophagy in cancer cell EMT and migration, offering opportunities for
therapeutic interventions to prevent invasion and metastasis.

32. Vasculogenic mimicry in glioblastoma and melanoma

Luca Colucci-D’Amato, Maria Teresa Gentile, Olga Pastorino

Laboratory of Molecular and Cellular Neuropathology, Department of Environmental, Biological and
Pharmaceutical Science and Technology, University of Campania “L. Vanvitelli”, Caserta 81100, Italy.

Background and aim: Neo-angiogenesis is the most studied mechanism of vascularization in tumors
and refers to sprouting of new blood vessels from pre-existing ones and it may be inhibited by natural
compounds. Vasculogenic mimicry (VM) is an alternative mechanisms of tumor vascularization providing
a means by which some tumors can escape anti-angiogenetic therapy. VM occurs in glioblastoma (GBM)
and melanoma, both tumors of neuroepithelial derivation. We investigated the role of REST/NRSF gene in
the pathophysiology of VM as well as the effects of compounds such as the histone deacetylase inhibitors
(HDACis) to interfere with VM.

Experimental procedure: To measure tube formation, cell migration, and invasion, we used: in vitro tube
formation assay on Matrigel, Boyden chamber migration assay, wound healing assay, invasion test, and
real-time migration monitoring. To measure cell viability, we used: MTT and trypan blue exclusion test. To
transfect cells, we used: lipofectamine standard protocol.

Results: We analyzed a number of GBM and melanoma cell lines. We found that the expression of REST
parallels the ability to migrate and to form tubes on Matrigel. Upon genetic or chemical down-regulation of
REST (via siRNA or dominant negative mutant or HDACi), we observed a decrease in migration ability as
well as tube formation. Finally, we found that different histone deacetylase inhibitors impair vasculogenic
mimicry from glioblastoma cells.

Conclusions: Our findings show that REST/NRSF gene is an important molecular player in the
pathophysiology of vasculogenic mimicry in GBM and melanoma and that HDAC inhibitors alone can
impair the formation of tubes from GBM cells.

33. Mouse tumor susceptibility alleles identify pathways for intervention in multiple myeloma

Beverly A. Mock

Laboratory of Cancer Biology & Genetics, Center for Cancer Research, National Cancer Institute, National
Institutes of Health, Bethesda, MD 20892, USA.