Page 46 - ebook

[A. Biochemistry/Molecular Biology] A-23

Senescent Tumor Cells from Colorectal Cancer Accelerate

Metastatic Niche Formation in the Liver

Soon Sang Park¹,²,⁵, Ga-Yeon Lee¹,⁵, Young-Kyoung Lee¹,⁵, So Hyun Park³,⁵, Chan Young Lee¹,²,⁵, Jang-

Hee Kim³,⁵, Yong Won Choi⁴,⁵, Tae Jun Park¹,²,⁵*

¹Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 16499, Korea,

²Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 16499, Korea, ³Department of
Pathology, Ajou University School of Medicine, Suwon 16499, Korea, ⁴Department of Hematology-Oncology, Ajou

University School of Medicine, Suwon 16499, Korea, ⁵Inflamm-Aging Translational Research Center, Ajou
University Medical Center, Suwon 16499, Korea

Cellular senescence implies permanent cell cycle arrest caused by various internal/external insults such as replicative

stress, hypoxia, cytotoxic agents, reactive oxygen species (ROS), etc. Among various senescent cell types in cancer
microenvironment, senescent tumor cells are regarded as a defense mechanism of our body against cancer

progression by inhibiting proliferation of cancer cells. 140 non-metastatic and metastatic colorectal cancer patients
were analyzed and p16INK4A-high patients are more frequently detected in metastatic CRC patients. Therefore, we

hypothesized that it is due to the microenvironmental difference of the pre-metastatic organ, called pre-metastatic
niche. To prove this hypothesis, extracellular matrix and immune microenvironment of p16INK4A negative (n=6)

and positive patients’ liver (n=69) was examined and compared. We found that only immune microenvironment,
not extracellular matrix, showed significant difference between two groups. Especially, bone marrow-derived

neutrophils are highly infiltrated in the p16INK4A positive patients’ liver. Subsequent in vivo mouse model showed
that the liver pre-learned by senescent conditioned medium recruited the significantly high number of CD11b

positive cells and most of them were neutrophils. Further study is needed how these neutrophils were homed to
the pre-metastatic site and how these recruited neutrophils assist cancer cell seeding in metastatic organ need to

be proven.