In metastatic ovarian cancer cells, Wnt/β-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.
‘Our findings are intriguing because few factors that regulate cancer polyploidy have been identified to date, and we have also provided a mechanistic rationale for targeting β-catenin or its downstream signalling molecules to decrease peritoneal dissemination associated with poor prognosis,’said Professor Alice WONG, Director (Interim) of the School of Biological Sciences, who led the research. The team plans to explore in more detail the signalling mechanisms that drive polyploidy in the metastatic cells, as this would greatly enhance the understanding of the genomically unstable disease.
About the research team
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.
Link of journal paper can be accessed from here: https://doi.org/10.1002/advs.202103230
More information about Professor Alice WONG’s work and her research team: https://www.awonglab.com/
港大與浸大的一個聯合研究揭示了巨噬細胞促進卵巢癌腹膜轉移的新機制。團隊指出，此項機制可透過抑制 metadherin 或 CEACAM1 來阻斷兩者的通訊，從而減少轉移。相關研究成果已在學術期刊《先進科學》（Advanced Science）上刊登。
研究團隊透過觀察人源化小鼠模型（immune humanized mice）上的分子分析發現，Wnt/β-catenin信號通路的提升可導致癌細胞在腹膜轉移。metadherin 和 CEACAM1 是兩種位於細胞的表面的蛋白，非常適合用作追踪癌細胞和臨床靶向。通過抑制 metadherin 或 CEACAM1 來阻斷巨噬細胞與癌細胞的通訊，能有效減少癌細胞的腹膜轉移。