Page 26 - HKSEMR2020 Programme book

Poster Presentation (Basic Science) Abstracts

P-cadherin-mediated tumor–mesothelium interaction induces

metabolic coupling as a determinant of metastatic outgrowth

Kun Wang, Jing Ma, Chi Bun Chan, Alice SZ Wong
School of Biological Sciences, University of Hong Kong, Pokfulam, Hong Kong.

Introduction / Background / Objectives: were observed upon co-culturing with mesothelial monolayers.
Mechanistically, P-cadherin positively modulated the expression of
Metabolic reprogramming is a hallmark of cancer. To survive
the harsh tumour microenvironment, cancer cells frequently lipogenic genes (ACLY, FASN, ACAT2) in cancer cells and induced
communicate with stromal cells to fulfill biosynthetic and neutral lipid accumulation (oil red O staining is a readout for neutral
bioenergetic demands. lipid accumulation). Concomitantly, the expression of P-cadherin
was positively related to that of four glycolysis-related genes
(GLUT1, HK2, Gpi and PGK1) in mesothelial cells. We demonstrated
Methods: that the lactate acid secreted by mesothelial cells fueled de novo
lipogenesis in cancer cells. As a proof of concept, targeting the
We analyzed metabolic profiles in ovarian cancer cells and lactate importer MCT1 was found to efficiently block the metabolic
mesothelial cells. Cytokine arrays, RNA-sequencing analysis, oil coupling between cancer and mesothelial cells, demonstrating a
red O staining and reverse transcription PCR were used. formidable strategy to inhibit peritoneal metastasis in vivo.

Results / Outcomes: Conclusion:
Here, we show for the first time that P-cadherin, a transmembrane Taken together, our results unravel a critical role of P-cadherin
adhesive protein, acts as a bidirectional activator of metabolic in metabolic coupling and identify lactate shuttling in the tumor-
coupling in the ovarian cancer-mesothelium niche. In cancer cells, mesothelium niche as a therapeutic window for ovarian peritoneal
elevated neutral lipid accumulation and increased proliferation metastasis.

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