16 May 2022
HKU Biologists Reveal a Novel Macrophages-mediated Mechanism that Promotes Peritoneal Metastasis of Ovarian Cancer, Providing Important Insights into Its Therapeutic Strategy
The research discovers that Wnt/b-catenin signalling in metastatic cells upregulates the expression of cancer cells metadherin and communicates with macrophages through CEACAM1. Image modified from original illustration of Adv. Sci. (Weinh) 2022; e21
Ovarian cancer is the leading cause of deaths among all gynaecological cancers. Over 70% of patients are diagnosed at an advanced stage with metastatic diseases. Peritoneal metastasis is very difficult to treat due to tumour heterogeneity and the dynamic interactions of cancer cells with the tumour microenvironment. The lack of suitable experimental models has been one significant obstacle to study the cellular and molecular mechanisms of this critical process, and the distinct interactions among different cancer cell subclones and tumour microenvironment are largely unknown using traditional bulk measurement.
Key findings: In metastatic ovarian cancer cells, Wnt/b-catenin signalling upregulates the expression of metadherin, which communicates with macrophages through CEACAM1, a carcinoembryonic antigen expressed by macrophages, suggesting that blockade of macrophage-tumour communications (by inhibiting either metadherin or CEACAM1) could greatly reduce peritoneal metastasis.
The team has made a key discovery of a potential driving mechanism for cancer cell polyploidy and genomic instability, which is initiated through direct interaction with macrophages. Targeting components of the molecular cascade identified in the study holds great therapeutic potential to disrupt polyploidisation of the cancer subclones that drive metastasis.
The research was co-led by Professor Alice Sze Tsai WONG (Director (Interim) of School of Biological Sciences, HKU), and Dr Jue SHI (Associate Professor, Department of Physics, Hong Kong Baptist University (HKBU)). Dr Sally Kit Yan TO (Postdoctoral Fellow, School of Biological Sciences, HKU), was the first author, with the assistance of Dr Maggie Kei Shuen TANG (Postdoctoral Fellow, Laboratory for Synthetic Chemistry and Chemical Biology, InnoHK; Honorary Research Associate, School of Biological Sciences, HKU) and Dr Yin TONG (Postdoctoral Fellow, Department of Pathology, HKU). Other collaborators include Dr Jiangwen ZHANG (Associate Professor, School of Biological Sciences, HKU), Dr Karen Kar Loen CHAN, Clinical Associate Professor, Department of Obstetrics and Gynecology, HKU), and Dr Philip Pun Ching IP (Clinical Associate Professor, Department of Pathology, HKU).
This work was supported by the Hong Kong Research Grant Council grants (17104820, 17141216, C4041-17G and C2006-17E) and ‘Laboratory for Synthetic Chemistry and Chemical Biology’ under the Health@InnoHK Program launched by Innovation and Technology Commission, HKSAR. Professor Alice WONG is a recipient of the Croucher Foundation Senior Research Fellowship.
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