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Page 14 of 27 J Cancer Metastasis Treat 2019;5:5 I http://dx.doi.org/10.20517/2394-4722.2018.108

of claudin-7 (AUC 0.659, P = 0.03). Genes involved in hypoxia and angiogenesis processes result strongly
associated to hematogenous recurrence (P = 0.012).

Conclusion: Claudin-7 decreased expression in primary tumor tissues is a significant predictor of distant
metastasis in HGSOC patients.

19. Glutamine synthetase-negative multiple myeloma cells secrete glutamate and shape the
bone marrow niche

Martina Chiu, Denise Toscani, Giuseppe Taurino, Fabrizio Accardi, Nicola Giuliani, Ovidio
Bussolati

Department of Medicine and Surgery (DiMeC), University of Parma, Parma 43121, Italy.

Altered metabolism, a hallmark of cancer, also impacts on non-cancer cells of tumor microenvironment,
driving them towards a pro-tumor behavior. In multiple myeloma (MM) patients, bone marrow glutamine
(Gln) is lowered, while glutamate (Glu) and ammonium increase. In most MM patients, Glutamine
Synthetase (GS), the enzyme that catalyzes Gln synthesis from Glu and ammonium, is lowered in neoplastic
plasma cells. GS is also down-regulated during normal osteoblast differentiation from mesenchymal stromal
cells (MSC). Since bone lesions of MM patients are characterized by impaired osteogenesis, we hypothesize
that MM cells negatively affect osteoblasts through the peculiar low-Gln, high-Glu bone marrow
microenvironment and the manipulation of GS expression in niche cells.

Human MM cell lines (HMCLs) and immortalized MSC were grown in Glu-free αMEM and used in mono-
or co-cultures. Gene expression was assessed at either mRNA and protein level. Amino acid levels were
determined with a colorimetric test (extracellular) and LC-MS/MS (intracellular).

Analysis of a dataset of 323-sample plasma cell dyscrasias indicated that GS expression is downregulated
+
during MM progression, with less than 20% MM patients with GS-positive CD138 cells. Also most HMCLs,
but not MM1.S and U266, have a negligible GS expression. While both low- and high-GS HMCLs exhibited
a high consumption of Gln and a comparable glutaminolysis, low-GS HMCLs exploited roughly 50% of Gln
to secrete Glu. Consistently, the activity of the Glu exchanger xCT was higher in low-GS MM cells. GS is
strongly induced in MSC when co-cultured with MM cells.

These preliminary results are consistent with the hypothesis that low GS expression, Gln addiction and Glu
secretion of MM cells are functional to osteoblastic differentiation impairment in the BM niche.

20. Evaluation of the interaction among HPV16 E6 and E7 oncoproteins and the DNA damage
sensor 53BP1 in 2D and 3D epithelial cultures by the proxymity ligation assay

Barbara Azzimonti, Diletta Francesca Squarzanti, Rita Sorrentino, Manuela Miriam Landini,
Andrea Chiesa.

University of Piemonte Orientale (UPO), School of Medicine, Department of Health Sciences, Via Solaroli 17,
Novara 28100, Italy.

Introduction: Human papillomaviruses (HPV) group several viruses are able to infect squamous stratified
epithelia and cause benign papillomas, warts and anogenital lesions. They also correlate to oropharyngeal