Research

Reproduced from Lee WJ, et al. J Exp Med. 2019;216(1):176-194. doi: 10.1084/jem.20181170

Omentum as the niche for peritoneal metastasis

The omentum is a fatty tissue that drapes from the stomach and contains a high abundance of immune structures called fat-associated lymphoid clusters (FALCs). FALCs are mainly composed of T cells, B cells and macrophages, and play a vital role in eliminating pathogens from the peritoeal fluid. Paradoxically, peritoneal cancer cells, including ovarian cancer cells that shed into the peritoneal fluid, are highly prone to implant in omental FALCs, and the mechanism by which omentum becomes dominated by metastatic tumors and cannot effectively defend against cancer cells is not clear.

Neutrophils as first-line defender that facilitate metastasis

Neutrophils are white blood cells that act as the first line of defense in response to infection and malignancy. Our research has identified that neutrophils mobilize into omental FALCs prior to metastasis in response to tumor-derived cytokines, and then extrude webs of chromatin fibers called neutrophil extracellular traps (NETs). NETs are part of innate-like immune responses that kill pathogens through entrapment, but they can also capture circulating tumor cells, thereby promoting omental metastasis.

Reproduced from Lee WJ, et al. J Exp Med. 2019;216(1):176-194. doi: 10.1084/jem.20181170

Identifying the heterogeneity of omental SVF in the pre-metastatic niche

Omental FALCs are maintained by complex interactions between various immune and non-immune stromal cells, which are essential for the functional maintenance of peritoneal cavity immunity. While research on the diversity of omental stromal vascular fraction (SVF) has recently emerged, the cellular heterogeneity and molecular mechanisms involved in the formation of the pre-metastatic niche remain poorly understood. Our findings indicate that the establishment of the pre-metastatic niche requires cooperative interactions among host stromal cell populations.

In this regard, our lab focuses on the following three key perspectives:

Elucidating the interactions between innate and adaptive immune cells.
Identifying the interactions between immune cells and non-immune stromal cells.
Investigating host factors that drive the formation of the pre-metastatic niche.

By determining cellular and molecular changes in the pre-metastatic omentum, our research will provide new insights that explain how these cellular dynamics contribute to compromised immune functions in omental FALCs and promote omental metastasis of peritoneal cancers.

Adapted from: Lee WJ, et al. Cancer Cell. 2025;43(1):69–85,

https://doi.org/10.1016/j.ccell.2024.12.004

Deciphering the molecular basis of heightened metastatic competence in the normal host microenvironment

Inflammatory responses are physiological processes that maintain homeostasis in response to external stimuli, but they also have various effects on the host microenvironment and play critical roles in regulating the onset and progression of various diseases, including cancer. Both acute inflammatory responses, such as that triggered by injury or traumatic stress, and chronic inflammation, as seen in aging or obesity, can accelerate the metastatic process by reshaping host microenivronments. In this context, our lab seeks to elucidate the host-derived factors that enhance metastatic competence at specific organ sites by analysis of molecular, biochemical, metabolic alterations within the host microenvironments.

Reproduced from Lee WJ, et al. J Exp Med. 2019;216(1):176-194. doi: 10.1084/jem.20181170

Our laboratory employs multidisciplinary approaches to investigate the mechanism of pre-metastatic niche formation, incorporating in vivo and in vitro models as well as high-dimensional immune profiling. Through this integrated strategy, our research aims to connect cellular heterogeneity with underlying molecular mechanisms, thereby identifying potential strategies for the early detection of metastatic tumors.

Google Sites

Report abuse